Diagnosis of deep venous thrombosis by phlebography and 99Tcsup (m)-Plasmin

International Nuclear Information System (INIS)

Edenbrandt, C-M.; Nilsson, J.; Ohlin, P.

1982-01-01

One hundred and thirty-four patients admitted to the medical emergency ward due to suspect deep venous thrombosis (DVT) were examined. The uptake of intravenously injected porcine 99 Tcsup (m)-plasmin was estimated in both legs. Thereafter, phlebography was performed using a high osmolar contrast medium. All phlebographies were evaluated independently. All patients with negative phlebography were examined after 3-5 days. The plasmin test and phlebography were repeated when called for. The sensivity of the plasmin test was 100% and the specificity 51% when compared to phlebography. The extension of the DVT as demonstrated by the plasmin test was similar to that determined by phlebography. Post-phlebographic trombosis was very rare. It is concluded that 99 Tcsup (m)-plasmin test is a rapid method, convenient to the patient and well suitable as a screening test. The results indicate that a negative plasmin test excludes DVT while a positive test necessitates additional examination by phlebography. (Authors)

Impacto del síndrome metabólico en la resistencia a la recanalización arterial y en el pronóstico de los pacientes con oclusión aguda de la arteria cerebral media tratados con activador tisular del plasminógeno

OpenAIRE

Dorado Bouix, Laura

2012-01-01

La recanalización arterial precoz es un punto clave para alcanzar un buen pronóstico funcional tras un ictus isquémico. El síndrome metabólico (SM) podría jugar un papel en la evolución de los pacientes con ictus isquémico tratados con activador tisular del plasminógeno (tPA) por vía sistémica (a) por su asociación a un estado protrombótico que podría interferir en la recanalización arterial inducida por tPA y (b) porque varias de las alteraciones metabólicas que acompañan al SM podrían contr...

Kinetic characterization of tissue-type plasminogen activator (t-PA) and t-PA deletion mutants

NARCIS (Netherlands)

de Vries, C. [=Carlie J. M.; Veerman, H.; Nesheim, M. E.; Pannekoek, H.

1991-01-01

The binding of t-PA to fibrin is mediated both by its "finger" (F) and its "kringle 2" (K2) domain. In addition, these domains are involved in the stimulation of t-PA activity by fibrin. We analyzed the kinetic characteristics of Glu-plasminogen activation by t-PA and a set of t-PA deletion mutants

Contact thermography, 99mTc-plasmin scintimetry and 99mTc-plasmin scintigraphy as screening methods for deep venous thrombosis following major hip surgery

DEFF Research Database (Denmark)

Christensen, S W; Wille-Jørgensen, P; Kjaer, L

1987-01-01

Fifty-six patients scheduled for total hip alloplasty were screened for deep venous thrombosis by means of 99mTc-plasmin scintimetry, 99mTc-plasmin scintigraphy and contact thermography. Investigations were performed on the seventh postoperative day, and a total of 112 legs were examined. Bilateral...

Diagnosis of deep venous thrombosis by phlebography and /sup 99/Tcsup (m)-Plasmin

Energy Technology Data Exchange (ETDEWEB)

Edenbrandt, C.M.; Nilsson, J.; Ohlin, P. (County Hospital, Helsingborg (Sweden). Dept. of Medicine, Diagnostic Radiology and Clinical Physology)

1982-01-01

One hundred and thirty-four patients admitted to the medical emergency ward due to suspected deep venous thrombosis (DVT) were examined. The uptake of intravenously injected porcine /sup 99/Tcsup (m)-plasmin was estimated in both legs. Thereafter, phlebography was performed using a high osmolar contrast medium. All phlebographies were evaluated independently. All patients with negative phlebography were examined after 3-5 days. The plasmin test and phlebography were repeated when called for. The sensivity of the plasmin test was 100% and the specificity 51% when compared to phlebography. The extension of the DVT as demonstrated by the plasmin test was similar to that determined by phlebography. Post-phlebographic trombosis was very rare. It is concluded that /sup 99/Tcsup (m)-plasmin test is a rapid method, convenient to the patient and well suitable as a screening test. The results indicate that a negative plasmin test excludes DVT while a positive test necessitates additional examination by phlebography.

Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

Science.gov (United States)

Swedberg, Joakim E; Harris, Jonathan M

2011-10-04

Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

Demonstration of 99mTc-labelled plasmin on the surface of ex vivo thrombi

International Nuclear Information System (INIS)

Tengborn, L.; Hedner, U.; Rohlin, M.; Stahlberg, F.

1982-01-01

In an vitro system using the Chandler model for the preparation of in vitro thrombi trace amounts of porcine or human 99mTc-labelled plasmin was found to adsorb to the surface of a preformed thrombus. A radioactive lining of the thrombus could be demonstrated using autoradiography after addition of 99mTc-labelled plasmin in concentrations of 0.04 - 0.07 or 0.4 - 0.7 CTA u/thrombus made from 2 ml whole blood (0.035 - 0.35 microM). The same pattern was found for porcine as for human plasmin. The presence of tranexamic acid in concentrations of 3 to 12 mM did not affect the binding of plasmin indicating that the plasmin binding to fibrin was independent of the lysine binding sites. Furthermore alpha 2-antiplasmin was demonstrated on/in the thrombus also when no plasmin was present indicating a binding of alpha 2-antiplasmin to the thrombus. The plasmin bound to the thrombus was proteolytically inactive. In order to obtain thrombolysis most of the alpha 2-antiplasmin in the surrounding medium had to be neutralized

Purification and characterization of mutant miniPlasmin for thrombolytic therapy

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Lin Xiaotao

2013-01-01

Full Text Available Abstract Background Previous animal studies by us and others have indicated that catheter-administered plasmin or its des-kringle derivatives may be more appropriate alternatives to plasminogen activators for treating thrombolytic diseases, since it has a very short serum half-life and therefore does not result in hemorrhaging. We have previously produced recombinant miniPlasmin (mPlasmin that was proven suitable for treating peripheral arterial occlusion in animal models. However, our previous results showed that non-specific cleavage at position K698 of mPlasmin during activation hindered the further development of this promising therapeutic candidate. In order to minimize or eliminate the non-specific cleavage problem, we performed saturation mutagenesis at the K698 position to develop a mutant form of mPlasmin for thrombolytic therapy. Methods We changed K698 to 16 other amino acids, with preferred E. coli codons. Each of these mutants were expressed in E. coli as inclusion bodies and then refolded, purified, and subsequently characterized by detailed kinetic assays/experiments/studies which identified highly active mutants devoid of non-specific cleavage. Results Activation studies indicated that at those conditions in which the wild type enzyme is cut at the non-specific position K698, the active mutants can be activated without being cleaved at this position. Conclusions From the above results, we selected two mutants, K698Q and K698N, as our lead candidates for further thrombolytic drug developments. The selected mutants are potentially better therapeutic candidates for thrombolytic therapy.

Effect of TPA and HTLV-1 Tax on BRCA1 and ERE controlled genes expression.

Science.gov (United States)

Jabareen, Azhar; Abu-Jaafar, Aya; Abou-Kandil, Ammar; Huleihel, Mahmoud

2017-07-18

Interference with the expression and/or functions of the multifunctional tumor suppressor BRCA1 leads to a high risk of breast and ovarian cancers. BRCA1 expression is usually activated by the estrogen (E2) liganded ERα receptor. Activated ERα is considered as a potent transcription factor which activates various genes expression by 2 pathways. A classical pathway, ERα binds directly to E2-responsive elements (EREs) in the promoters of the responsive genes and a non-classical pathway where ERα indirectly binds with the appropriate gene promoter. In our previous study, HTLV-1Tax was found to strongly inhibit ERα induced BRCA1 expression while stimulating ERα induced ERE dependent genes. TPA is a strong PKC activator which found to induce the expression of HTLV-1. Here we examined the effect of TPA on the expression of BRCA1 and genes controlled by ERE region in MCF-7 cells and on Tax activity on these genes. Our results showed strong stimulatory effect of TPA on both BRCA1 and ERE expression without treatment with E2. Tax did not show any significant effect on these TPA activities. It seems that TPA activation of BRCA1 and ERE expression is dependent on PKC activity but not through the NFκB pathway. However, 53BP1 may be involved in this TPA activity because its overexpression significantly reduced the TPA stimulatory effect on BRCA1 and ERE expression. Additionally, our Chip assay results probably exclude possible involvement of ERα pathway in this TPA activity because TPA did not interfere with the binding of ERα to both BRCA1 promoter and ERE region.

PVD following plasmin but not hyaluronidase: implications for combination pharmacologic vitreolysis therapy.

Science.gov (United States)

Wang, Zhi-Liang; Zhang, Xi; Xu, Xun; Sun, Xiao-Dong; Wang, Fang

2005-01-01

To study whether intravitreal injection of plasmin + hyaluronidase safely induces posterior vitreous detachment (PVD). Rabbits were randomized into three groups: (A) 20 rabbits, intravitreal injection of plasmin 1 U + hyaluronidase 20 U in balanced salt solution (BSS) 0.1 mL into one eye; (B) 12 rabbits, plasmin alone; (C) 12 rabbits, hyaluronidase alone. The fellow eye of each rabbit was injected BSS 0.1 mL. In Group A, scanning electron microscopy (SEM) was done in four rabbits at 0.5 hour and in four rabbits at 1 hour. After 7 days, all the remaining 36 rabbits received electroretinography, SEM was examined in eight of each group, and immunohistochemistry was done in four of each group. SEM disclosed the eyes of Group A had complete PVD (8/8), Group B partial PVD (7/8), and Group C (8/8) and all the control eyes (24/24) no PVD after 7 days. Partial PVD was found in 4/4 at 0.5 hour and complete PVD was seen in 3/4 at 1 hour in Group A. Immunohistochemistry showed that the amounts of laminin and fibronectin in the vitreoretinal interface were decreased in Group A and B versus the control eyes (P 0.05). Electroretinography showed no changes in any group (P >0.05). Vitreous injection of plasmin + hyaluronidase induced complete PVD with no obvious toxicity. Plasmin induced partial PVD, but hyaluronidase had no effects.

Suppression of endothelial t-PA expression by prolonged high laminar shear stress

International Nuclear Information System (INIS)

Ulfhammer, Erik; Carlstroem, Maria; Bergh, Niklas; Larsson, Pia; Karlsson, Lena; Jern, Sverker

2009-01-01

Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low (≤1.5 dyn/cm 2 ) or high (25 dyn/cm 2 ) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30% of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.

Activation of carbon monoxide by (Me3tpa)Rh and (Me3tpa)Ir

NARCIS (Netherlands)

Dzik, W.I.; Smits, J.M.M.; Reek, J.N.H.; de Bruin, B.

2009-01-01

Cationic iridium and rhodium carbonyl complexes supported with the tetradentate N-donor ligand Me(3)tpa (Me(3)tPa = N,N,N-tri(6-methyl-2-pyridylmethyl)amine) were synthesized. Their structures were investigated using X-ray diffraction, NMR, and IR, and their redox properties were probed using cyclic

Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+

International Nuclear Information System (INIS)

Winters, K.J.; Eisenberg, P.R.; Jaffe, A.S.; Santoro, S.A.

1990-01-01

The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125 I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca 2+ , conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca 2+ . The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation

Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin

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Jonathan H. Foley

2016-03-01

Full Text Available Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC. In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution.

Plasmin digest of κ-casein as a source of antibacterial peptides.

Science.gov (United States)

Sedaghati, Marjaneh; Ezzatpanah, Hamid; Boojar, Masoud Mashhadi Akbar; Ebrahimi, Maryam Tajabadi; Aminafshar, Mehdi

2014-05-01

This study investigated the antibacterial properties of plasmin, the plasmin hydrolysis of bovine κ-casein and the fractions (named κC1, κC2, κC3, κC4, and κC5) liberated from it using RP-HPLC. The target bacteria were Escherichia coli, Staphylococcus aureus (pathogenic), Lactobacillus casei and Lactobacillus acidophilus (probiotic). Three peptides (kC1, kC3, and kC4) were found to have antibacterial activity, with κC3 peptide being the most active. The plasmin digest of bovine κ-casein proved to be stronger than any of its fractions in terms of antibacterial potential. Measurement of the minimum inhibitory concentration (MIC) showed that Gram-positive bacteria are generally more sensitive to antibacterial activity than Gram-negative bacteria. The MIC of nisin, as a bacteriocin peptide, was also measured. The three antibacterial peptides were identified using LC-Mass. The molecular mass of kC1, kC3, and kC4 corresponded to the f(17-21), f(22-24), and f(1-3) of bovine κ-casein, respectively. It was also found that the positive charge and hydrophobicity of a peptide are not key factors in antibacterial activity. On the whole, the present study demonstrated that the plasmin digest of κ-casein has a high antibacterial potential and can be considered as a natural antibacterial agent in the food chain.

Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia

NARCIS (Netherlands)

Renckens, Rosemarijn; Weijer, Sebastiaan; de Vos, Alex F.; Pater, Jennie M.; Meijers, Joost C.; Hack, C. Erik; Levi, Marcel; van der Poll, Tom

2004-01-01

Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To

TPA-inducible proteins may account for sensitivity to promotion of transformation

International Nuclear Information System (INIS)

Hirano, K.; Smith, B.; Colburn, N.H.

1986-01-01

The preneoplastic JB6 mouse epidermal cell system includes cell lines sensitive (P + ) or resistant (P - ) to tumor promoter induced neoplastic transformation. The authors investigated whether a difference in TPA-inducible proteins may explain this differential sensitivity. The synthesis of a 39 Kd cytoplasmic protein (Major Excreted Protein) was TPA-inducible, but to a similar extent in both P + and P - cells. TPA stimulated phosphorylation but not synthesis of the previously described stress protein pp80 in both P + and P - cells from 1 to 5 hr after treatment. Pulse labelling of P + and P - cells with 35 S-methionine revealed a TPA dependent P + specific transient increase in the synthesis of 58Kd protein. Induction was observed at 1 hr, and returned to basal levels by 4 hr and 20 hr, in nuclear and cytoplasmic fractions, respectively. This protein is not phosphorylated in response to TPA treatment. P + cells differ from P - cells in one or more genes that specify sensitivity to promotion of transformation, designated pro genes. Antibodies to three peptides representing the pro-1 open reading frame were used in immunoprecipitation and Western blotting to isolate the pro-1 gene product. A 43 Kd protein was immunologically responsive to the pro-1 peptide antibodies, and showed an increased signal 40 min after TPA treatment. Since the predicted molecular weight of a pro-1 gene product is only 7 Kd, the possibility of a modification of the protein by poly(ADP-ribosylation) or glycosylation is being investigated

The nature of interactions between tissue-type plasminogen activator and platelets

International Nuclear Information System (INIS)

Torr, S.R.; Winters, K.J.; Santoro, S.A.; Sobel, B.E.

1990-01-01

To elucidate interactions responsible for inhibition of aggregation of platelets in platelet-rich plasma (PRP) harvested from whole blood preincubated with t-PA, experiments were performed with PRP and washed platelets under diverse conditions of preincubation. Both ADP and collagen induced aggregation were inhibited in PRP unless aprotinin had been added to the preincubated whole blood concomitantly with t-PA. However, in washed platelets prepared after the same exposure aggregation was intact. When washed platelets were supplemented with fibrinogen degradation products (FDPs) in concentrations simulating those in whole blood preincubated with t-PA, aggregation induced with either ADP or collagen was inhibited. Thus, the inhibition in PRP depended on generation of FDPs by activated plasminogen. The functional integrity of surface glycoprotein (GP) IIb/IIIa receptors in washed platelets was documented by autoradiography after SDS-PAGE of surface labeled GPs and by fibrinogen binding despite preincubation of the whole blood or washed platelets themselves with t-PA and plasminogen as long as exogenous calcium (greater than or equal to 0.1 microM) was present. In contrast, when calcium was absent, the platelet GP IIb/IIIa receptor was rendered susceptible to degradation by plasmin, and aggregation was inhibited by preincubation at 37 degrees C even if aprotinin was present when aggregation was being assayed. These observations reconcile disparate results in the literature from studies in vivo and in vitro by demonstrating that inhibition of aggregation of platelets in PRP and in whole blood reflects indirect effects of plasminogen activation rather than direct effects of t-PA or plasmin on the platelets themselves

Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

DEFF Research Database (Denmark)

Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G

2014-01-01

diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

Estatus de la concentración de homocisteina y de algunos componentes de la fibrinólisis: Eslabón trombogénico en la homocistinuria clásica

Directory of Open Access Journals (Sweden)

S. A. Castañeda

2001-07-01

Full Text Available El objetivo de este estudio fue determinar el estatus de las concentraciones de homociteína (Hcy, inhibidor del activador del plasminógeno tipo 1 (PAI-1 y activador tisular del plasminógeno (tPA en pacientes con homocistinuria clásica, en familiares de éstos y en una población control sana.

Comparison between 99Tcm-porcine plasmin and 99Tcm-labelled erythrocytes in diagnosis of deep vein thrombosis

Energy Technology Data Exchange (ETDEWEB)

Edenbrandt, C.M.; Dahlstroem, J.A.; Nilsson, J.; Ohlin, P.

1984-06-01

In 20 patients with suspect deep venous thrombosis (DVT), scintillation detector measurements were performed over each leg during the first 60 min after intravenous injection of 99Tcm-porcine plasmin. Thereafter, 99Tcm-labelled autologous erythrocytes were injected i.v. and repeat measurements were performed. Finally, scintillation camera images of both legs were obtained. Phlebography was used as a reference method. A close relationship was found between the scintillation detector measurements, both in patients with DVT (n . 11) and in patients without DVT (n . 9). Thus, 99Tcm-plasmin is not specifically bound to the thrombus. Rather the clinical utility of the test depends mainly on circulatory changes secondary to the thrombus. Scintillation camera images of 99Tcm-erythrocytes in the legs were not useful for diagnosis of DVT in the calves but showed a high specificity for DVT in the popliteal and femoral veins.

Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

DEFF Research Database (Denmark)

Svenningsen, Per; Bistrup, Claus; Friis, Ulla G

2009-01-01

stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC gamma subunit...

IMPACTS OF TISSUE-TYPE PLASMINOGEN ACTIVATOR (TPA ON NEURONAL SURVIVAL

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Arnaud eChevilley

2015-10-01

Full Text Available Tissue-type plasminogen activator (tPA a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central nervous system, tPA displays both neurotrophic and neurotoxic effects. How can the protease mediate such opposite functions remain unclear but several hypotheses have been proposed. These include an influence of the degree of maturity and/or the type of neurons, of the level of tPA, of its origin (endogenous or exogenous or of its form (single chain tPA versus two chain tPA. In this review, we will provide a synthetic snapshot of our current knowledge regarding the natural history of tPA and discuss how it sustains its pleiotropic functions with focus on excitotoxic/ischemic neuronal death and neuronal survival.

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.

Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion.

Science.gov (United States)

Castiblanco-Valencia, Mónica Marcela; Fraga, Tatiana Rodrigues; Pagotto, Ana Helena; Serrano, Solange Maria de Toledo; Abreu, Patricia Antonia Estima; Barbosa, Angela Silva; Isaac, Lourdes

2016-05-01

Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N- and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. Copyright © 2016. Published by Elsevier GmbH.

Determinación de los parámetros cinéticos de la plasmina porcina y comparación con la humana = Porcine plasmin: determination of kinetic parameters and comparison with human plasmin

Directory of Open Access Journals (Sweden)

Arbeláez Ramírez, Luis Fernando

2012-04-01

Full Text Available El plasminógeno es el zimógeno de la plasmina, enzima relacionada con la disolución del coágulo sanguíneo. Estudios con plasminas de diferentes especies animales han demostrado mayor afinidad que la plasmina humana por sustratos análogos hechos exclusivamente para ella. Así lo confirman la activación y cinética del sistema plasminógeno/plasmina porcino, que hasta el presente no se habían determinado ni comparado con el humano. En este trabajo se utilizaron, para la purificación del plasminógeno, cromatografía de afinidad y cambio iónico; se utilizó urocinasa para la activación del plasminógeno a plasmina y se determinaron los parámetros cinéticos con el sustrato cromógeno S-2251. Los terminales-N se determinaron por el método de degradación de Edman. La plasmina porcina demostró mayor afinidad (Km por el sustrato que la plasmina humana, 1,55 y 5,3 mM respectivamente, mientras que la plasmina humana mostró mayor velocidad de conversión del sustrato a producto (0,1 UA/ seg que la porcina (0,033 UA/seg. Los terminales-N se diferenciaron en los aminoácidos 1 y 3, DPPDDY (porcino y EPLDDY (humano.

PEGylated DX-1000: Pharmacokinetics and Antineoplastic Activity of a Specific Plasmin Inhibitor

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Laetitia Devy

2007-11-01

Full Text Available Novel inhibitors of the urokinase-mediated plasminogen (plg activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pin (Ki = 99 pM. When tested in vitro, DX-1000 blocks plasminmediated pro-matrix metal loproteinase-9 (proMMP-9 activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor (~ 7 kDa exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogenactivated protein kinase (MAPK in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

Tissue Plasminogen Activator (tPA) Mediates Neurotoxin-Induced Cell Death and Microglial Activation

National Research Council Canada - National Science Library

Tsirka, Styliani-Anna

2000-01-01

.... In mice lacking tPA (tPA-/-), neurons are resistant to neurotoxic death. Delivery of tPA into tPA mice restores susceptibility to neuronal death, indicating that tPA is neurotoxic in the context of excitotoxic injury...

Topical anti-inflammatory activity of Polygonum cuspidatum extract in the TPA model of mouse ear inflammation

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Wicker Louise

2008-02-01

Full Text Available Abstract Background This study tested the ability of a characterized extract of Polygonum cuspidatum (PCE to inhibit mouse ear inflammation in response to topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA. Methods A 50% (wt:vol ethanolic solution of commercial 200:1 PCE was applied to both ears of female Swiss mice (n = 8 at 0.075, 0.15, 0.3, 1.25 and 2.5 mg/ear 30 min after TPA administration (2 μg/ear. For comparison, 3 other groups were treated with TPA and either 1 the vehicle (50% ethanol alone, 2 indomethacin (0.5 mg/ear, or 3 trans-resveratrol (0.62 mg/ear. Ear thickness was measured before TPA and at 4 and 24 h post-TPA administration to assess ear edema. Ear punch biopsies were collected at 24 h and weighed as a second index of edema. Myeloperoxidase activity was measured in each ear punch biopsy to assess neutrophil infiltration. Results PCE treatment at all doses significantly reduced ear edema compared to the TPA control. The PCE response was dose-dependent and 2.5 mg PCE significantly inhibited all markers of inflammation to a greater extent than indomethacin (0.5 mg. MPO activity was inhibited at PCE doses ≥ 1.25 mg/ear. Trans-resveratrol inhibited inflammation at comparable doses. Conclusion PCE inhibits development of edema and neutrophil infiltration in the TPA-treated mouse ear model of topical inflammation.

Tissue Plasminogen Activator (tPA) Mediates Neurotoxin-Induced Cell Death and Microglial Activation

National Research Council Canada - National Science Library

Tsirka, Styliani-Anna

2001-01-01

.... In mice lacking tPA (tPA-/1), neurons are resistant to neurotoxic death. Delivery of tPA into tpA-/- mice restores susceptibility to neuronal death, indicating that tPA is neurotoxic in the context of excitotoxic injury...

An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells.

Science.gov (United States)

Rockwell, W B; Ehrlich, H P

1991-02-01

Serum-free culture medium harvested from endothelial cell monolayer cultures derived from human scars and dermis was examined for inhibition of fibrinolysis using a fibrin plate assay. Human cultured fibroblasts and smooth muscle cells did not produce any detectable inhibitory activity. The inhibitor is spontaneously released from the cultured endothelial cells over time. In the fibrin plate assay of plasmin-induced fibrinolysis, one nonsteroidal antiinflammatory (NSAI) drug, ibuprofen, was demonstrated to antagonize the inhibition of fibrinolysis. The antagonistic activity of ibuprofen appears unrelated to its NSAI drug activity because other NSAI drugs such as indomethacin and tolmetin have minimal antagonistic activity. Heating the cultured endothelial cells to 42 degrees C stimulates greater release of the inhibitor in a shorter period of time. This plasmin inhibitor, which is produced by endothelial cells, may contribute to postburn vascular occlusion, leading to secondary progressive necrosis in burn-traumatized patients.

Initial experience with TPA as a tumour marker in ovarian malignancy

International Nuclear Information System (INIS)

Dalen, A. van; Favier, J.; Eastham, W.N.

1984-01-01

The Tissue Polypeptide Antigen (TPA) and Carcinoembryonic Antigen (CEA) content of serum were estimated in samples taken from 21 patients with malignant ovarian tumours. The patients were followed for variable period ranging from 6 to 22 months and the TPA and CEA levels were estimated after debulking operations and courses of CHAP-5 therapy. The relative success of the operation and/or treatment was reflected in an appropriate alteration of the serum TPA level. CEA levels remained more or less stationary. The serum TPA levels of 13 of the 21 patients, irrespective of the tumour type, differentiation or stage of tumour growth, exhibited a good concordance with the clinical observations at second look operations. The one patient with a disseminated form of adenoacanthoma failed to show an elevation of the TPA levels and 7 patients continue to have a constantly elevated TPA levels but as yet no clinical evidence of recurrent or metastatic disease. (orig.) [de

An enzyme-immunobinding assay for fast screening of expression of tissue plasminogen activator cDNA in E. coli

International Nuclear Information System (INIS)

Tang, J.C.T.; Li, S.H.

1984-01-01

Tissue plasminogen activator (TPA) has been isolated from normal human tissues and certain human cell lines in culture. The enzyme is a serine protease which converts an inactive zymogen, plasminogen to plasmin, and causes lysis of fibrin clots. The high affinity of TPA for fibrin indicates that it is a potential thrombolytic agent and is superior to urokinase-like plasminogen activators. Recently, TPA has been cloned and expressed in E. coli. Using TPA as a model protein, the authors report here the development of a direct, sensitive enzyme-immunoassay for the screening of a cDNA expression library using specific antibodies and peroxidase-labeled second antibody

Polypyrrole layered SPEES/TPA proton exchange membrane for direct methanol fuel cells

Energy Technology Data Exchange (ETDEWEB)

Neelakandan, S.; Kanagaraj, P. [PG & Research Department of Chemistry, Polymeric Materials Research Lab, Alagappa Government Arts College, Karaikudi 630003 (India); Sabarathinam, R.M. [Functional Material Division, Central Electrochemical Research Institute, Karaikudi 630006 (India); Nagendran, A., E-mail: nagimmm@yahoo.com [PG & Research Department of Chemistry, Polymeric Materials Research Lab, Alagappa Government Arts College, Karaikudi 630003 (India)

2015-12-30

Graphical abstract: - Highlights: • A series of Ppy layered SPEES/TPA composite membranes were prepared. • SPEES/TPA-Ppy hybrid membranes displayed efficient methanol resistance than Nafion 117. • SPEES/TPA-Ppy4 membrane exhibits highest relative selectivity of 2.86 × 104 S cm{sup 3} s. • Increasing Ppy layer on membrane surface reduces the leaching out of tungstophosphoric acid. - Abstract: Hybrid membranes based on sulfonated poly(1,4-phenylene ether ether sulfone) (SPEES)/tungstophosphoric acid (TPA) were prepared. SPEES/TPA membrane surfaces were modified with polypyrrole (Ppy) by in situ polymerization method to reduce the TPA leaching. The morphology and electrochemical property of the surface coated membranes were studied by SEM, AFM, water uptake, ion exchange capacity, proton conductivity, methanol permeability and tensile strength. The water uptake and the swelling ratio of the surface coated membranes decreased with increasing the Ppy layer. The surface roughness of the hybrid membrane was decreased with an increase in Ppy layer on the membrane surface. The methanol permeability of SPEES/TPA-Ppy4 hybrid membrane was significantly suppressed and found to be 2.1 × 10{sup −7} cm{sup 2} s{sup −1}, which is 1.9 times lower than pristine SPEES membrane. The SPEES/TPA-Ppy4 membrane exhibits highest relative selectivity (2.86 × 10{sup 4} S cm{sup −3} s) than the other membrane with low TPA leaching. The tensile strength of hybrid membranes was improved with the introduction of Ppy layer. Combining their lower swelling ratio, high thermal stability and selectivity, SPEES/TPA-Ppy4 membranes could be a promising material as PEM for DMFC applications.

Polypyrrole layered SPEES/TPA proton exchange membrane for direct methanol fuel cells

International Nuclear Information System (INIS)

Neelakandan, S.; Kanagaraj, P.; Sabarathinam, R.M.; Nagendran, A.

2015-01-01

Graphical abstract: - Highlights: • A series of Ppy layered SPEES/TPA composite membranes were prepared. • SPEES/TPA-Ppy hybrid membranes displayed efficient methanol resistance than Nafion 117. • SPEES/TPA-Ppy4 membrane exhibits highest relative selectivity of 2.86 × 104 S cm"3 s. • Increasing Ppy layer on membrane surface reduces the leaching out of tungstophosphoric acid. - Abstract: Hybrid membranes based on sulfonated poly(1,4-phenylene ether ether sulfone) (SPEES)/tungstophosphoric acid (TPA) were prepared. SPEES/TPA membrane surfaces were modified with polypyrrole (Ppy) by in situ polymerization method to reduce the TPA leaching. The morphology and electrochemical property of the surface coated membranes were studied by SEM, AFM, water uptake, ion exchange capacity, proton conductivity, methanol permeability and tensile strength. The water uptake and the swelling ratio of the surface coated membranes decreased with increasing the Ppy layer. The surface roughness of the hybrid membrane was decreased with an increase in Ppy layer on the membrane surface. The methanol permeability of SPEES/TPA-Ppy4 hybrid membrane was significantly suppressed and found to be 2.1 × 10"−"7 cm"2 s"−"1, which is 1.9 times lower than pristine SPEES membrane. The SPEES/TPA-Ppy4 membrane exhibits highest relative selectivity (2.86 × 10"4 S cm"−"3 s) than the other membrane with low TPA leaching. The tensile strength of hybrid membranes was improved with the introduction of Ppy layer. Combining their lower swelling ratio, high thermal stability and selectivity, SPEES/TPA-Ppy4 membranes could be a promising material as PEM for DMFC applications.

ESTIMASI ALIRAN AIR LINDI TPA BANTAR GEBANG BEKASI MENGGUNAKAN METODA SP

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Syamsu Rosid

2012-02-01

Full Text Available Air lindi merupakan limbah sampah organik yang biasanya diproduksi dari sampah rumah tangga. Pencemaran air tanah (groundwater oleh air lindi menjadi ancaman yang serius bagi masyarakat. Penduduk Bantar Gebang, Bekasi merasa terancam kehidupannya dengan adanya tempat pembuangan akhir (TPA sampah yang dikirim dari DKI Jakarta. Beberapa penduduk di sekitar TPA mengeluhkan bahwa air sumurnya agak bau dan tidak lagi terasa segar. Untuk mengetahui seperti apa polusi air lindi yang terjadi, ke arah mana dan sudah sejauh mana sebarannya, dan memetakan daerah resiko tinggi terkena polusi maka telah dilakukan pengukuran geolistrik metoda self potential (SP di sebelah Tenggara dan Selatan daerah TPA Bantar Gebang, Bekasi. Dari data SP diketahui bahwa aliran air tanah bawah permukaan di daerah tersebut berarah Selatan ke Utara. Meskipun lokasi TPA berada di Utara daerah penelitian, limbah air lindi diduga telah mencemari air tanah bawah permukaan hingga radius ratusan meter dari lokasi TPA. Penyebaran air limbah ini  diperkirakan melalui proses osmosis, mekanisme kapilaritas dan proses elektrokinetik.   Kata kunci: air lindi, metoda SP, TPA Bantar Gebang.

SOSIAL EKONOMI KOMUNITAS PEMULUNG DI TPA LUBUK MINTURUN

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sumarni

2012-10-01

Full Text Available This research aims to expose the social economic of Pemulung community in TPA Lubuk Minturun. This research applies qualitative research. The informan of this research are Pemulung in TPA Air Dingin Kelurahan Balai Gadang, Kecamatan Koto Tangah Kota Padang by using snowball sampling. The datas are gathered by observing, interviewing, and documenting. In purpose of keeping the data authenticity, it is needed the explanations from the credible information (credible and realiable from the selected items (Mestika Zed, 1999. The research show that the low level of education of Pemulung does not affect toward their income in TPA Air Dingin because what they do, does not need certain skills and education. Their strategies to gather things are to search them form early morning and they involve all of family members in term of “Maraok”. While in marketing strategy, they sell the thing they have got to the collector (Lapak owner who wants to buy more expensive or they sell whenever the price is higher. Pemulung in TPA Air Dingin have never got direct financial security from the government of Padang, so that it affects to the structural poverty. The way of live they have cause such a structural poverty. They are used to be relax and feel comfort with their work system. Pemulung in TPA Air Dingin do not want to change the system that they have made, so that still live in the circle of cultural poverty.

Penyisihan Limbah Organik Air Lindi TPA Jatibarang Menggunakan Koagulasi-Flokulasi Kimia

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Arya Rezagama

2016-12-01

Full Text Available Air lindi yang meresap ke dalam tanah yang berpotensi bercampur dengan air tanah sehingga menimbulkan pencemaran tanah, air tanah dan air permukaan. Komposisi limbah lindi dari berbagai TPA berbeda-beda bergantung pada musim, jenis limbah, umur TPA. Proses dalam TPA menghasilkan molekul organik recalcitrant yang ditunjukkan dengan rendahnya rasio BOD/COD dan tingginya nilai NH3-N. Belum optimalnya pengolahan air lindi di Jatibarang membutuhkan pretreatment sebagai bentuk upaya alternatif dalam proses pengolahan air lindi sebelum masuk ke dalam proses aerated lagun. Penelitian ini bertujuan untuk menganalisa pengaruh koagulan kimia pada penyisihan bahan organik air lindi TPA Jatibarang. Penelitian dilakukan pada bulan April- Agustus 2016. Karaktersitik air lindi TPA Jatibarang termasuk dalam kategori "moderately stable" dan lindi muda. Penyisihan bahan organik dengan menggunakan kuagulan kimia FeCl3 dan Al2SO4 menunjukkan nilai yang cukup signifikan untuk parameter COD, BOD, TSS. Penggunaan dosis optimal terjadi pada 16 g/L FeCl3 serta 16 g/L Al2SO4 dapat menurunkan nilai COD sebesar 51% dan 65%, BOD sebesar 50% dan 56%, dan TSS sebesar 24% dan 21%. Perubahan nilai pH akibat penambahan koagulan berpengaruh positif terhadap tingkat penyisihan, namun memberikan dampak negatif yaitu buih yang cukup banyak. Penurunan beban organik menguntungkan bagi sistem pengolahan lindi eksisting TPA Jatibarang.  [Title: Removal of Lindi Water Organic Waste of TPA Jatibarang using Chemical Coagulation- Floculation] Leachate grounding into the soil that potentially could mix with the groundwater caused contamination of soil, groundwater and surface water. The composition of waste landfill leachate from the various location is depending on the season, the type of waste, and landfill age. Process in the TPA produces recalcitrant organic molecules as indicated by the low ratio of BOD/COD and NH3-N high value. The ineffective treatment of leachate at Jatibarang

Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke

DEFF Research Database (Denmark)

Saver, Jeffrey L; Goyal, Mayank; Bonafe, Alain

2015-01-01

BACKGROUND: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addit...

Promotion of Wound Healing by an Agonist of Adenosine A2A Receptor Is Dependent on Tissue Plasminogen Activator.

Science.gov (United States)

Montesinos, M Carmen; Desai-Merchant, Avani; Cronstein, Bruce N

2015-12-01

Impaired wound healing, as it occurs in diabetes mellitus or long-term corticoid treatment, is commonly associated with disability, diminished quality of life, and high economic costs. Selective agonists of the A2A receptor subtype of adenosine, an endogenous regulator of inflammation, promote tissue repair in animal models, both healthy and with impaired healing. Plasmin-mediated proteolysis of fibrin and other matrix proteins is essential for cell migration at sites of injury. Since adenosine A2A receptor activation increases plasminogen activator release from macrophages and mast cells, we studied the effect of a selective agonist, CGS-21680, on full-thickness excisional wound closure in wild-type, urokinase plasminogen activator (uPA)-deficient, and tissue plasminogen activator (tPA)-deficient mice. Wound closure was impaired in tPA- and uPA-deficient mice as compared with wild-type mice, and topical application of CGS-21680 significantly increased the rate at which wounds closed in wild-type mice and uPA-deficient mice, but not in tPA-deficient mice. Immunostaining of tissue sections showed that tPA was present in endothelial cells and histiocytes by day 3 post-wound and also by day 6. In contrast, uPA was more prominent in these cell types only by day 6 post-wound. Our results confirm that plasminogen activation contributes to wound repair and are consistent with the hypothesis that adenosine A2A receptor activation promotes wound closure by a mechanism that depends upon tPA, but not uPA. Moreover, our results suggest that topical adenosine A2A receptor agonists may be useful in promotion of wound closure in patients with impaired wound healing.

Plasma levels of plasmin-antiplasmin-complexes are predictive for small abdominal aortic aneurysms expanding to operation-recommendable sizes

DEFF Research Database (Denmark)

Lindholt, Jes Sanddal; Jørgensen, B; Fasting, H

2001-01-01

Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall. Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms (AAAs).......Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall. Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms (AAAs)....

The story of an exceptional serine protease, tissue-type plasminogen activator (tPA).

Science.gov (United States)

Hébert, M; Lesept, F; Vivien, D; Macrez, R

2016-03-01

The only acute treatment of ischemic stroke approved by the health authorities is tissue recombinant plasminogen activator (tPA)-induced thrombolysis. Under physiological conditions, tPA, belonging to the serine protease family, is secreted by endothelial and brain cells (neurons, astrocytes, microglia, oligodendrocytes). Although revascularisation induced by tPA is beneficial during a stroke, research over the past 20 years shows that tPA can also be deleterious for the brain parenchyma. Thus, in this review of the literature, after a brief history on the discovery of tPA, we reviewed current knowledge of mechanisms by which tPA can influence brain function in physiological and pathological conditions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The Complement Binding and Inhibitory Protein CbiA of Borrelia miyamotoi Degrades Extracellular Matrix Components by Interacting with Plasmin(ogen

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Ngoc T. T. Nguyen

2018-02-01

Full Text Available The emerging relapsing fever spirochete Borrelia (B. miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD. More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen. Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.

Dimerized plasmin fragment D as a potential biomarker to predict successful catheter-directed thrombolysis therapy in acute deep vein thrombosis.

Science.gov (United States)

Luo, Chien-Ming; Wu, I-Hui; Chan, Chih-Yang; Chen, Yih-Sharng; Yang, Wei-Shiung; Wang, Shoei-Shen

2015-10-01

The value of dimerized plasmin fragment D in the clinical monitoring during the catheter-directed thrombolysis in patients with acute deep vein thrombosis is not known. Dimerized plasmin fragment D levels in 24 patients with acute deep vein thrombosis undergoing catheter-directed thrombolysis were prospectively evaluated. The plasma dimerized plasmin fragment D level was measured serially before and at every 12 h during catheter-directed thrombolysis for 24 h. Technical success was defined as restoration of patency and flow with less than 50% residual thrombus by surveillance rotational venography. Technical success was achieved in 79.2% (19 of 24) of the treated limbs after catheter-directed thrombolysis. In univariate analysis, there was significant elevation of the dimerized plasmin fragment D at 12th h after starting the catheter-directed thrombolysis (P fragment D to predict successful catheter-directed thrombolysis was determined as 18.4 µg/ml at the 12th h after starting the catheter-directed thrombolysis with sensitivity 0.8 and specificity 0.8 (P = 0.03). It was further validated in multivariate logistic regression analysis (odds ratio: 14.38; 95% CI: 1.22-169.20; P = 0.03). Catheter-directed thrombolysis is safe and effective for restoration of blood flow in patients with acute deep vein thrombosis. Dimerized plasmin fragment D value greater than 18.4 µg/ml at the 12th h after starting catheter-directed thrombolysis had a high predictive rate of greater than 50% lysis at the end of catheter-directed thrombolysis. © The Author(s) 2014.

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.

REVITALISASI TPA PEH KABUPATEN JEMBRANA SEBAGAI TEMPAT PENGOLAHAN SAMPAH TERPADU

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Angelina Puspita Sandy

2015-06-01

Full Text Available Waste management in Jembrana District, had been handled by the Environmental Sanitation Department, which in 2012 the amount of garbage in Jembrana District it’s about 684.80 m3. The amount of garbage was large and continues to grow up every day, thus feared that TPA Peh will overload. This problem encourages the needed for Integrated Waste Sites Planning in TPA Peh, where it will accept the loads of Jembrana garbage. The Integrated Waste Site Planning in TPA Peh requires some studies, such as study of the technical aspects, financial aspects and environmental aspects. Based on technical analysis it was known that the garbage of Jembrana district in TPA Peh amounted to 150.56 m3/day. Recovery factor value was 80.33% with 19.87% residue. If this large amount of garbage is not processed, then TPA Peh predicted will be overloud in November 2015. By Integrated Waste Site Planning which is only the residue that wasted on landfill, then it could be extended the lifespan of the landfill until 9 (nine years and 3 (three month. Required area in the application of Integrated Waste Site Planning in TPA Peh is 13.701 m2. The total cost of investment in the implementation of the Integrated Waste Site in TPA Peh is Rp. 12.331.282.000.00. Total operational cost is Rp. 5.811.760.000, while the revenue potential of recycling such as composting and stalls selling stuff in 2022 is Rp. 18.390.154.291.56. Net Present Value (NPV obtained positive value of Rp. 13.933.193.788 with a value of IRR is 45,23% and B / C ratio is 1,159. Environmental analysis on TPA Peh Jembrana by analysis of well water quality around the landfill, is known that most of the physical and chemical parameters are still under the quality standard. Biological parameters are still above the water quality standards based on Permenkes No. 416.Menkes/Per/IX/1990. From the analysis of landfill leachate water quality parameters known for Total Suspended Solids (TSS, Ammonium-free, BOD, COD and

Modified TPA-supported removable pontic

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Abhay Kumar Jain

2014-01-01

Full Text Available Missing posterior teeth or necessary asymmetric orthodontic extraction may lead to migration, tilting of the adjacent teeth, and supra-eruption of the opposing teeth along with compromised esthetics. The modified TPA supported removable pontic acts as an esthetic pontic during orthodontic space closure.

Radioimmunoassay of an early plasmin degradation product of human fibrinogen, 'fragment A', and its clinical application

Energy Technology Data Exchange (ETDEWEB)

Takagi, K; Kawai, T [Jichi Medical School, Kawachi, Tochigi (Japan)

1978-02-01

Upon the plasmin digestion of human fibrinogen, an early cleavage product, which has been designated as fragment A, was isolated, and to study the action of plasmin in the circulation, radioimmunoassay for fragment A was carried out. This assay used rabbit immune serum obtained by injection of fragment A mixed with complete Freund's adjuvant, and fragment A was labelled with /sup 125/I using the Chloramin-T method. In 20 normal healthy donors its serum level was 3.57 +- 1.62..mu..g/ml (mean+-SD), and it was increased significantly in certain diseases, such as acute leukemias, candiovascular disorders, malignancies, renal failure, systemic lupus erythematosus and sepsis.

Simatik : Aplikasi Simulasi Bank Soal Tes Potensi Akademik (TPA Berbasis Multi Platform

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Made Hendra Yudha Saputra

2017-01-01

Full Text Available Abstrak---Penelitian ini bertujuan untuk : (1 menghasilkan rancang bangun dan implementasi Simatik : Aplikasi Simulasi Bank Soal Tes Potensi Akademik (TPA Berbasis Multi Platform, (2 Mengetahui respon dari Pengguna terhadap Simatik : Aplikasi Simulasi Bank Soal Tes Potensi Akademik (TPA Berbasis Multi Platform. Dalam perancangannya, aplikasi ini akan menggunakan arsitektur client-server untuk melakukan proses pertukaran data. Perancangan dilakukan dengan menggunakan model fungsional berupa UML. Model fungsional berupa UML tersebut diimplementasikan dalam sebuah framework yaitu Phonegap dengan bahasa pemrograman HTML5. Untuk mengetahui respon terhadap Simatik : Aplikasi Simulasi Bank Soal Tes Potensi Akademik (TPA Berbasis Multi Platform ini diperoleh dengan menggunakan metode angket. Hasil akhirnya yaitu berupa Aplikasi Simatik berbasis Multi Platform yang dapat diinstall pada perangkat mobile untuk digunakan dalam latihan soal-soal yang terkait dengan Tes Potensi Akademik (TPA. Berdasarkan hasil uji usability, aplikasi Simatik berbasis Multi Platform ini mendapatkan persentase hasil sebesar 95,6 % dengan kategori sangat baik yang berarti dalam pengoperasiannya aplikasi ini mudah untuk digunakan dan dapat berfungsi sesuai dengan fungsi seharusnya. Kata Kunci : Phonegap, Multi Platform, Client Server, Mobile, Tes Potensi Akademik (TPA, Simatik   Abstract--- This research is purpose to : (1 produce generate design and implementation Simatik : Aplikasi Simulasi Bank Soal Tes Potensi Akademik (TPA Berbasis Multi Platform (2 To knowing the response of users to Simatik : Aplikasi Simulasi Bank Soal Tes Potensi Akademik (TPA Berbasis Multi Platform. In its design, this application will use the client-server architecture to make the exchange process of data. The design were done by using a functional model UML form. The functional model UML form is implemented within a framework that is phonegap with HTML 5 programming languages. To determine the

PENGEMBANGAN WEB TPA MIFTAHUL JANNAH MENUJU TPA YANG MANDIRI DAN SEJAHTERA

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Hidayatulah Himawan

2015-04-01

Full Text Available Growth and development of young children should be guided from the beginning . Education is carried out continuously should be directed to a positive destination . Garden Education Al - Quran ( TPA is one means of education that provides the fundamentals of the science of understanding the religion ( Islam . Jannah is a landfill Miftahul education institutions , from time to time with the level of activity that the higher activity , requires a medium for the board to be able to provide opportunities for the students to improve the ability and quality of human resources, especially in the management of information systems towards a more independent and TPA prosperous , using IT as a tool to help increase performance . The process of quality improvement and the ability to lead an independent and prosperous landfill , by submitting any reports and conditions in the landfill Miftahul Jannah quickly and easily accessible by anyone . Report and the information addressed to the board and donors involved directly or indirectly . Conducted an online web system development to lay any existing reports . In addition , an increase in capacity through training to use online web administrators or managers of the system at the landfill Miftahul Jannah . This is done so that the ability of life skills can be used as a tool for the managers in the landfill Miftahul Jannah for entrepreneurship can be independently and enhance confidence .

Determining Human Clot Lysis Time (in vitro with Plasminogen/Plasmin from Four Species (Human, Bovine, Goat, and Swine

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Omaira Cañas Bermúdez

2015-05-01

Full Text Available Cardiovascular disease is the leading cause of death worldwide, including failures in the plasminogen/plasmin system which is an important factor in poor lysis of blood clots. This article studies the fibrinolytic system in four species of mammals, and it identifies human plasminogen with highest thrombolysis efficiency. It examines plasminogen from four species (human, bovine, goat, and swine and identifies the most efficient one in human clot lysis in vitro. All plasminogens were identically purified by affinity chromatography. Human fibrinogen was purified by fractionation with ethanol. The purification of both plasminogen and fibrinogen was characterized by one-dimensional SDS-PAGE (10%. Human clot formation in vitro and its dissolution by plasminogen/plasmin consisted of determining lysis time from clot formation to its dilution. Purification of proteins showed greater than 95% purity, human plasminogen showed greater ability to lyse clot than animal plasminogen. The article concludes that human plasminogen/plasmin has the greatest catalysis and efficiency, as it dissolves human clot up to three times faster than that of irrational species.

I Failed the edTPA

Science.gov (United States)

Kuranishi, Adam; Oyler, Celia

2017-01-01

In this article, co-written by a teacher and a professor, the authors examine possible explanations for why Adam (first author), a New York City public school special educator, failed the edTPA, a teacher performance assessment required by all candidates for state certification. Adam completed a yearlong teaching residency where he was the special…

Beginning Teachers' Perceptions of the California Teaching Performance Assessment (TPA)

Science.gov (United States)

Campbell, Conni; Ayala, Carlos Cuauhtémoc; Railsback, Gary; Freking, Frederick W.; McKenna, Corey; Lausch, David

2016-01-01

The teaching performance assessment (TPA) seeks to measure the knowledge, skills, and competencies of teachers during the credential phase of their training. The TPA was introduced in California in 2004 with programs piloting it and then became mandatory for candidates enrolling in preliminary programs in 2008. Although California has multiple…

Programme for the simulation of the TPA-i 1001 computer on the CDC-1604-A computer

International Nuclear Information System (INIS)

Belyaev, A.V.

1976-01-01

The basic features and capacities of the program simulating the 1001 TPA-i computer with the help of CDC-1604-A are described. The program is essentially aimed at translation of programs in the SLAHG language for the TPA-type computers. The basic part of the program simulates the work of the central TPA processor. This subprogram consequently performs the actions changing in the necessary manner the registers and memory states of the TPA computer. The simulated TPA computer has subprograms-analogous of external devices, i.e. the ASR-33 teletype, the FS 1501 tape reader, and the FACIT perforator. Work according to the program takes 1.65 - 2 times less time as against the work with TPA with the minimum set of external equipment [ru

Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice

DEFF Research Database (Denmark)

Almholt, Kasper; Lund, L.R.; Rygaard, Jørgen

2005-01-01

A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now find that uPA deficiency alone significantly reduces metastasis...... >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume...

Beta-amyloidolysis and glutathione in Alzheimer's disease

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Lasierra-Cirujeda J

2013-04-01

Full Text Available J Lasierra-Cirujeda,1 P Coronel,2 MJ Aza,3 M Gimeno2 1CM Hematológico SC, Logroño, La Rioja, Spain; 2Tedec-Meiji Farma, SA, Alcalá de Henares, Madrid, Spain; 3Pharmaceutical Act, Ministry of Health, Regional Government, La Rioja, Spain Abstract: In this review, we hypothesized the importance of the interaction between the brain glutathione (GSH system, the proteolytic tissue plasminogen activator (t-PA/plasminogen/plasmin system, regulated by plasminogen activator inhibitor (PAI-1, and neuroserpin in the pathogenesis of Alzheimer's disease. The histopathological characteristic hallmark that gives personality to the diagnosis of Alzheimer's disease is the accumulation of neurofibroid tangles located intracellularly in the brain, such as the protein tau and extracellular senile plaques made primarily of amyloidal substance. These formations of complex etiology are intimately related to GSH, brain protective antioxidants, and the proteolytic system, in which t-PA plays a key role. There is scientific evidence that suggests a relationship between aging, a number of neurodegenerative disorders, and the excessive production of reactive oxygen species and accompanying decreased brain proteolysis. The plasminogen system in the brain is an essential proteolytic mechanism that effectively degrades amyloid peptides ("beta-amyloidolysis" through action of the plasmin, and this physiologic process may be considered to be a means of prevention of neurodegenerative disorders. In parallel to the decrease in GSH levels seen in aging, there is also a decrease in plasmin brain activity and a progressive decrease of t-PA activity, caused by a decrease in the expression of the t-PA together with an increase of the PAI-1 levels, which rise to an increment in the production of amyloid peptides and a lesser clearance of them. Better knowledge of the GSH mechanism and cerebral proteolysis will allow us to hypothesize about therapeutic practices. Keywords: glutathione

Stroke, tPA, and Physician Decision-Making

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... MD Steven Karceski, MD Stroke, tPA, and physician decision-making Dominic Hovsepian, BS Steven Karceski, MD WHAT DID ... has not been carefully studied is the physician ’ s decision-making process. It was because of this that Dr. ...

Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration.

Science.gov (United States)

Qiu, Weiming; Lei, Mingxing; Zhou, Ling; Bai, Xiufeng; Lai, Xiangdong; Yu, Yu; Yang, Tian; Lian, Xiaohua

2017-06-01

Regeneration of hair follicles relies on activation of hair follicle stem cells during telogen to anagen transition process in hair cycle. This process is rigorously controlled by intrinsic and environmental factors. 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, accelerates reentry of hair follicles into anagen phase. However, it is unclear that how TPA promotes the hair regeneration. In the present study, we topically applied TPA onto the dorsal skin of 2-month-old C57BL/6 female mice to examine the activity of hair follicle stem cells and alteration of signaling pathways during hair regeneration. We found that refractory telogen hair follicles entered anagen prematurely after TPA treatment, with the enhanced proliferation of CD34-positive hair follicle stem cells. Meanwhile, we observed Akt signaling was activated in epidermis, hair infundibulum, bulge and hair bulb, and Wnt signaling was also activated after hair follicle stem cells proliferation. Importantly, after overexpression of DKK1, a specific Wnt signaling inhibitor, the accelerated reentry of hair follicles into anagen induced by TPA was abolished. Our data indicated that TPA-induced hair follicle regeneration is associated with activation of Akt and Wnt/β-catenin signaling.

The University Supervisor, edTPA, and the New Making of the Teacher

Science.gov (United States)

Donovan, Martha K.; Cannon, Susan O.

2018-01-01

As university supervisors at a large, urban university in the southern US, we examined the ways that the Education Teacher Performance Assessment (edTPA) shaped the pedagogic relationships and decision-making processes of our students and ourselves during the spring of 2016. We situated this study of edTPA within the framework of critical policy…

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

Science.gov (United States)

Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

2015-07-01

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of Serum Fibrinogen, Plasminogen, α2-Anti-Plasmin, and Plasminogen Activator Inhibitor Levels (PAI and Their Correlation with Presence of Retinopathy in Patients with Type 1 DM

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Sefika Burcak Polat

2014-01-01

Full Text Available Background. Diabetic retinopathy (DR is the leading cause of blindness in the world. Retinopathy can still progress despite optimal metabolic control. The aim of the study was to determine whether different degrees of DR (proliferative or nonproliferative were associated with abnormally modulated hemostatic parameters in patients with T1DM. Method. 52 T1DM patients and 40 healthy controls were enrolled in the study. Patients were subdivided into three categories. Group I was defined as those without retinopathy, group II with NPRP, and group III with PRP. We compared these subgroups with each other and the control group (Group IV according to the serum fibrinogen, plasminogen, alpha2-anti-plasmin (α2-anti-plasmin, and PAI. Results. We detected that PAI-1, serum fibrinogen, and plasminogen levels were similar between the diabetic and control groups (P=0.209, P=0.224, and P=0.244, resp., whereas α2-anti-plasmin was higher in Groups I, II, and III compared to the control group (P<0.01, P<0.05, and P<0.001, resp.. There was a positive correlation between serum α2-anti-plasmin and HbA1c levels (r=0,268, P=0.031. Conclusion. To our knowledge there is scarce data in the literature about α2-anti-plasmin levels in type 1 diabetes. A positive correlation between α2-anti-plasmin with HbA1c suggests that fibrinolytic markers may improve with disease regulation and better glycemic control.

Adenylate cyclase regulation in the spermatogenic cell plasma membrane: Modulating effects of TPA and TCDD

International Nuclear Information System (INIS)

Beebe, L.E.

1989-01-01

This research was designed to compare the effects of TPA, a phorbol ester, and TCDD in a spermatogenic cell population, a target of TCDD toxicity. Membrane-bound adenylate cyclase activity was used an index of membrane function, and was quantified by the amount of 32 P-cAMP formed from 32 P-ATP following chromatographic separation. Exposure to male germ cells in-vitro to TPA and TCDD followed by direct measurement of enzyme activity was used to investigate the potential of each agent to perturb membrane function. TPA and TCDD consistently inhibited adenylate cyclase activity at the levels of G s -catalytic unit coupling and hormone-receptor activation, as measured by the stimulation of enzyme activity by concomitant addition of forskolin and GTP and FSH and GTP, respectively. The effect on coupling required at least 60 minutes of exposure to TPA or TCDD. Concentration-response curves demonstrated a progressive desensitization with increasing TPA concentration, while TCDD exhibited consistent inhibition over the same concentration range

Shock Hugoniot measurements on Ta to 0.78 TPa

International Nuclear Information System (INIS)

Froeschner, K.E.; Lee, R.S.; Chau, H.H.; Weingart, R.C.

1983-01-01

Symmetric impact shock Hugoniot measurements have been made on Ta with an electrically exploded foil gun system. The results obtained to date for the Hugoniot of Ta cover the range 0.19 to 0.78 TPa (impact velocities from 4.0 to 9.7 km/s) and agree with data obtained by other researchers to within 2.7% rms. Recent improvements in the system include electromagnetic shielding of impactor and target, continuous measurement of impactor velocity with a Fabry-Perot interferometer and computer-aided analysis of shot film. Conservative extrapolation from current operating conditions indicate that pressures of 1.1 to 1.5 TPa could be achieved with little difficulty

The Accelerated Procedure for Electrical Work (TPA)

CERN Document Server

Coelingh, G J

2000-01-01

The accelerated procedure for electrical work [in French: Travaux électriques selon Procédure Accélérée (TPA)] was introduced in October 1996. It allows the contractor to carry out minor electrical installation jobs (about 350 a year) independently. The special features of the TPA are that the number of hours to be worked is limited to 16 and the cost to less than 1000 CHF. This procedure has substantial advantages for both the requesters and ST division. Firstly, the requester benefits from direct contact with the contractor, prompt action and simplified invoicing. In addition, ST division, relieved of ordinary minor work, can concentrate on larger-scale projects and can take advantage of a simplified system of administration. The author sets out the course of the procedure, its advantages and drawbacks, the statistics and the results of a satisfaction questionnaire. This procedure could be adapted and extended to other operations linked to future contracts.

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

NARCIS (Netherlands)

Nieuwenhuizen, W.; Voskuilen, M.; Hermans, J.

1982-01-01

The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the

MANAJEMEN RISIKO OPERASIONAL DAN PEMELIHARAAN TEMPAT PEMBUANGAN AKHIR (TPA REGIONAL BANGLI DI KABUPATEN BANGLI

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I W Wedana Yasa

2013-07-01

Full Text Available To obtain the maximum and sustainable advantage it needs to carry out the operational and maintenance (OP activities of TPA. It is necessary to maintain the Bangli Regional TPA so that it will give maximum and sustainable advantages. This study was aimed at identifying various major risks which may interfere with the TPA operating and maintenance so that mitigation can be done and to determine the risk ownership. The collected data were analyzed using descriptive qualitative method through the following stages: the risks were identified, the risks were evaluated, the risks were coped with, and the risk ownership could be identified. The risks identified totaled 72 consisting of: 9 (12.5% risks which were under the unacceptable category, 16 (22.22% risks which were under the acceptable category, and 1 (1.39% risk which was under the negligible category. The major risks amounted to 55 risks (76.39%, included the obstacle to establishing the institution which was fully responsible for the operating and maintenance of the Bangli Regional TPA, the limited amounts of funds allocated by the central government, the provincial government, and the regency governments which were integrated into the Regional TPA, the obstacle to creating an affiliation between the government and the private institutions, and other risks. The risk mitigation was done by avoiding risks, reducing risks, and transferring risks starting from the institutional, regulation and financial aspects, and technical and non technical problems. Most risk ownerships were the responsibility of the Bangli Regional TPA management.

Tissue-type plasminogen activator contributes to remodeling of the rat ductus arteriosus

Science.gov (United States)

Saito, Junichi; Nicho, Naoki; Zheng, Yun-Wen; Ichikawa, Yasuhiro; Ito, Satoko; Umemura, Masanari; Fujita, Takayuki; Ito, Shuichi; Taniguchi, Hideki; Asou, Toshihide; Masuda, Munetaka; Ishikawa, Yoshihiro

2018-01-01

Aims The ductus arteriosus (DA) closes after birth to adapt to the robust changes in hemodynamics, which require intimal thickening (IT) to occur. The smooth muscle cells of the DA have been reported to play important roles in IT formation. However, the roles of the endothelial cells (ECs) have not been fully investigated. We herein focused on tissue-type plasminogen activator (t-PA), which is a DA EC dominant gene, and investigated its contribution to IT formation in the DA. Methods and results ECs from the DA and aorta were isolated from fetal rats using fluorescence-activated cell sorting. RT-PCR showed that the t-PA mRNA expression level was 2.7-fold higher in DA ECs than in aortic ECs from full-term rat fetuses (gestational day 21). A strong immunoreaction for t-PA was detected in pre-term and full-term rat DA ECs. t-PA-mediated plasminogen-plasmin conversion activates gelatinase matrix metalloproteinases (MMPs). Gelatin zymography revealed that plasminogen supplementation significantly promoted activation of the elastolytic enzyme MMP-2 in rat DA ECs. In situ zymography demonstrated that marked gelatinase activity was observed at the site of disruption in the internal elastic laminae (IEL) in full-term rat DA. In a three-dimensional vascular model, EC-mediated plasminogen-plasmin conversion augmented the IEL disruption. In vivo administration of plasminogen to pre-term rat fetuses (gestational day 19), in which IT is poorly formed, promoted IEL disruption accompanied by gelatinase activation and enhanced IT formation in the DA. Additionally, experiments using five human DA tissues demonstrated that the t-PA expression level was 3.7-fold higher in the IT area than in the tunica media. t-PA protein expression and gelatinase activity were also detected in the IT area of the human DAs. Conclusion t-PA expressed in ECs may help to form IT of the DA via activation of MMP-2 and disruption of IEL. PMID:29304073

Simultaneous assay for plasmin and DNase using radiolabeled human fibroblasts on microcarriers

International Nuclear Information System (INIS)

Boswell, G.S.; Dimitrijevich, S.D.; Gracy, R.W.

1989-01-01

A critical step in tissue and wound repair is the removal of eschar--accumulation of denatured cellular and extracellular macromolecules. Enzymatic debridement using a combination of plasmin (fibrinolysin) and DNase has been successfully utilized on a variety of types of wounds. Monitoring the activity of these enzymes by measuring the rate of fibrinolysis, or by viscometric changes due to DNA hydrolysis, is exceedingly cumbersome, time consuming, and, at best, only semiquantitative. Although spectrophotometric assays using synthetic substrates offer several advantages, they do not allow extrapolation of the data to the more complex natural substrates encountered in vivo. We have, therefore, developed an in vitro radioisotopic assay for the simultaneous and quantitative measurement of the hydrolytic activity of both plasmin and DNase. Double labeled ([3H]thymidine, [14C]leucine) human dermal fibroblasts grown on microcarrier beads are utilized as sources of nucleic acid and protein substrates. The assay meets all the criteria of analytical validity, is sensitive and rapid, and is amenable to adaptation for analysis of other hydrolytic enzymes. The method offers a direct evaluation of the enzymatic debridement of wounds using actual human cellular substrates. Moreover, the microcarriers provide a greatly increased surface area for cell attachment and growth, are amenable to rapid separation from the cells by simple mechanical methods, and are ideally suited to analytical manipulations

Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice.

Science.gov (United States)

Sánchez, G M; Re, L; Giuliani, A; Núñez-Sellés, A J; Davison, G P; León-Fernández, O S

2000-12-01

We compared the protective abilities of Mangifera indica L. stem bark extract (Vimang) 50-250 mgkg(-1), mangiferin 50 mgkg(-1), vitamin C 100 mgkg(-1), vitamin E 100 mgkg(-1)and beta -carotene 50 mgkg(-1)against the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative damage in serum, liver, brain as well as in the hyper-production of reactive oxygen species (ROS) by peritoneal macrophages. The treatment of mice with Vimang, vitamin E and mangiferin reduced the TPA-induced production of ROS by the peritoneal macrophages by 70, 17 and 44%, respectively. Similarly, the H(2)O(2)levels were reduced by 55-73, 37 and 40%, respectively, when compared to the control group. The TPA-induced sulfhydryl group loss in liver homogenates was attenuated by all the tested antioxidants. Vimang, mangiferin, vitamin C plus E and beta -carotene decreased TPA-induced DNA fragmentation by 46-52, 35, 42 and 17%, respectively, in hepatic tissues, and by 29-34, 22, 41 and 17%, in brain tissues. Similar results were observed in respect to lipid peroxidation in serum, in hepatic mitochondria and microsomes, and in brain homogenate supernatants. Vimang exhibited a dose-dependent inhibition of TPA-induced biomolecule oxidation and of H(2)O(2)production by peritoneal macrophages. Even if Vimang, as well as other antioxidants, provided significant protection against TPA-induced oxidative damage, the former lead to better protection when compared with the other antioxidants at the used doses. Furthermore, the results indicated that Vimang is bioavailable for some vital target organs, including liver and brain tissues, peritoneal exudate cells and serum. Therefore, we conclude that Vimang could be useful to prevent the production of ROS and the oxidative tissue damages in vivo. Copyright 2000 Academic Press.

Estatus de la concentración de homocisteína y de algunos componentes de la fibrinolisis: eslabón trombogénico en la homocistinuria clásica

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Beatriz Meneses

2001-04-01

Full Text Available Aumentos moderados o severos de Homocisteína (Hcy en la sangre y alteraciones en la fibrinólisis, están estrechamente relacionados
con enfermedad cardiovascular. En la homocistinuria clásica, los
pacientes experimentan un estado de hipercoagulabilidad y con mucha frecuencia eventos tromboembólicos, que son su principal causa de mortalidad. El objetivo de este estudio fue determinar el estatus de la concentraciones de Hcy, Inhibidor del Activador del Plasminógeno tipo 1 (PAI-1 y Activador tisular del Plasminógeno (tPA en pacientes con homocistinuria clásica, en familiares de éstos y en una población control sana.

Thrombolysis by intravenous tissue plasminogen activator (t-PA). Current status and future direction

International Nuclear Information System (INIS)

Tanahashi, Norio

2009-01-01

In Japan, the intravenous tissue plasminogen activator (t-PA) Alteplase (0.6 mg/kg) administration of the within 3 h of the onset of acute ischemic stroke was approved for therapeutic use in the year 2006. t-PA induces thrombolysis in patients with acute ischemic stroke, and this method has gradually gained recognition among physicians and the general population. However, the number of patients who were treated using Alteplase is low (4,000-5,000 patients/year), and this figure accounts for only 2-3% of the annual number of cases of ischemic stroke. There is little doubt that Alteplase treatment is a potentially effective modality for some patients with acute ischemic stroke. The post-marketing surveillance of 4,749 Japanese patients treated using Alteplase showed that 33% of the patients had modified Rankin scale (mRS) scores of 0-1, 17% of patients died and 4.5% presented with symptomatic intracerebral hemorrhage (ICH); these results were comparable to those from other countries. The expansion of the therapeutic time window has been a matter of concern. The investigators of the European Cooperative Acute Stroke Study (ECASS) have reported that there was significant improvement in the clinical outcomes of patients with acute ischemie stroke when Alteplase was administered 3-4.5 h after the onset of the symptoms. Mismatches in perfusion- and diffusion-weighted (DW) magnetic resonance imaging (MRI) images have been used for selecting patients 3 h after the onset of symptoms, and the findings from MRI, dwimages (DWI) and MR angiography are practical predictors of t-PA therapy within 3 h of onset. The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan study showed that local intra-arterial fibrinolysis is effective in patients with embolic MCA occlusion within 6 h of the onset of symptoms. Combining the initiation of intravenous t-PA administration with further intra-arterial fibrinolysis or mechanical thrombolectomy may improve the

Thrombolysis by intravenous tissue plasminogen activator (t-PA). Current status and future direction

Energy Technology Data Exchange (ETDEWEB)

Tanahashi, Norio [Saitama Medical Univ., International Medical Center, Hidaka, Saitama (Japan)

2009-01-15

In Japan, the intravenous tissue plasminogen activator (t-PA) Alteplase (0.6 mg/kg) administration of the within 3 h of the onset of acute ischemic stroke was approved for therapeutic use in the year 2006. t-PA induces thrombolysis in patients with acute ischemic stroke, and this method has gradually gained recognition among physicians and the general population. However, the number of patients who were treated using Alteplase is low (4,000-5,000 patients/year), and this figure accounts for only 2-3% of the annual number of cases of ischemic stroke. There is little doubt that Alteplase treatment is a potentially effective modality for some patients with acute ischemic stroke. The post-marketing surveillance of 4,749 Japanese patients treated using Alteplase showed that 33% of the patients had modified Rankin scale (mRS) scores of 0-1, 17% of patients died and 4.5% presented with symptomatic intracerebral hemorrhage (ICH); these results were comparable to those from other countries. The expansion of the therapeutic time window has been a matter of concern. The investigators of the European Cooperative Acute Stroke Study (ECASS) have reported that there was significant improvement in the clinical outcomes of patients with acute ischemie stroke when Alteplase was administered 3-4.5 h after the onset of the symptoms. Mismatches in perfusion- and diffusion-weighted (DW) magnetic resonance imaging (MRI) images have been used for selecting patients 3 h after the onset of symptoms, and the findings from MRI, dwimages (DWI) and MR angiography are practical predictors of t-PA therapy within 3 h of onset. The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan study showed that local intra-arterial fibrinolysis is effective in patients with embolic MCA occlusion within 6 h of the onset of symptoms. Combining the initiation of intravenous t-PA administration with further intra-arterial fibrinolysis or mechanical thrombolectomy may improve the

Natural history of TPA-untreated minor stroke in the North Dublin population stroke study

LENUS (Irish Health Repository)

Marnane, M

2011-05-01

Introduction: Current guidelines recommend caution when considering emergency tissue plasminogen activator (tPA) therapy for patients with minor neurological deficits. However few data exist regarding the “natural history” (without tPA) of stroke in unselected population-based cohorts. We sought to evaluate the risk of long term disability in “minor stroke” patients.\\r\

Expression of uPA, tPA, and PAI-1 in Calcified Aortic Valves

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Najlah Kochtebane

2014-01-01

Full Text Available Purpose. Our physiopathological assumption is that u-PA, t-PA, and PAI-1 are released by calcified aortic valves and play a role in the calcification of these valves. Methods. Sixty-five calcified aortic valves were collected from patients suffering from aortic stenosis. Each valve was incubated for 24 hours in culture medium. The supernatants were used to measure u-PA, t-PA, and PAI-1 concentrations; the valve calcification was evaluated using biphotonic absorptiometry. Results. Aortic stenosis valves expressed normal plasminogen activators concentrations and overexpressed PAI-1 (u-PA, t-PA, and PAI-1 mean concentrations were, resp., 1.69 ng/mL ± 0.80, 2.76 ng/mL ± 1.33, and 53.27 ng/mL ± 36.39. There was no correlation between u-PA and PAI-1 (r=0.3 but t-PA and PAI-1 were strongly correlated with each other (r=0.6. Overexpression of PAI-1 was proportional to the calcium content of the AS valves. Conclusions. Our results demonstrate a consistent increase of PAI-1 proportional to the calcification. The overexpression of PAI-1 may be useful as a predictive indicator in patients with aortic stenosis.

Ativador do Plasminogênio Tecidual (tPA/ Fator Neurotrófico Derivado do Cérebro (BDNF e a Consolidação da Memória/ Tissue Plasminogen Activator (tPA/ Brain Derived Neurotrophic Factor (BDNF and the Consolidation of Memory

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Rodolfo Souza de Faria

2014-09-01

Full Text Available O Fator Neurotrófico Derivado do Cérebro (BDNF participa de processos de plasticidade sináptica subjacentes à aprendizagem e memória. Esta proteína possui diversas isoformas, sendo a isoforma BDNF-maduro envolvida nas mudanças neuronais da memória. Além disso, foi demonstrado que a consolidação da memória aversiva depende do Ativador do Plasminogênio Tecidual (tPA, enzima que estabelece a formação do BDND-maduro na fenda sináptica garantindo os processos neuroplásticos da aprendizagem. Para esta revisão de literatura, foram selecionados 37 trabalhos, dentre eles 36 artigos científicos e 1 livro. A consolidação da memória requer a ativação gênica para síntese de novas proteínas, sendo a tPA e o BDNF algumas das principais moléculas neuronais expressas no hipocampo, amigdala, córtex frontal em diferentes momentos após o início da aprendizagem, ativando uma série de eventos moleculares que levam ao aumento da expressão de outras proteínas, garantindo assim a regulação fina da plasticidade neuronal necessária para a memória. The Brain Derived Neurotrophic Factor (BDNF participates in synaptic plasticity processes underlying learning and memory. This protein has several isoforms, mature-BDNF one isoform involved in neuronal memory changes. Furthermore, it was demonstrated that the consolidation of aversive memory depends on the tissue plasminogen activator (tPA, an enzyme that establishes the formation of the mature BDND-synaptic cleft, guaranteeing neuroplastic learning processes. For this literature review, we selected 37 works, including 36 scientific articles and one book. The consolidation of memory for gene activation requires new protein synthesis, tPA and BDNF and some of the major neuronal molecules expressed in the hippocampus, amygdala, frontal cortex at different times after the start of learning, activating a series of molecular events leading the increased expression of other proteins, thereby

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen, produced by plasmin (fragments X)

NARCIS (Netherlands)

Nieuwenhuizen, W.; Gravesen, M.

1981-01-01

Early plasmin degradation products (X fragments) of human fibrinogen were prepared in the presence of calcium-ions or EGTA, and purified on Sepharose 6B-CL. X fragments were characterized with respect to amino-terminal amino acids, polypeptide-chain composition, anticlotting properties and

Differential diagnostic value of combined detection of serum CA153, CEA and TPA levels in patients with breast tumor

International Nuclear Information System (INIS)

Ding Wei

2007-01-01

Objective: To assess the differential diagnostic value of combined detection of serum CA153, CEA and TPA levels in patients with breast tumor. Methods: Serum levels of CA153, CEA and TPA were measured with RIA in 269 patients with breast tumor and 150 controls. Results: The serum levels of CA153, CEA and TPA in patients with breast cancer were significantly higher than those in the patients with benign breast tumor and controls. The positive rate of CA153 was 63.8% in the patients with breast cancer and that of CEA and TPA was 22.4% and 62.1% respectively, with combined detection of CA153 and CEA, the positive rate was 69.8%, with CA153 and TPA combined, the positive rate was 87.1%, with the three marker combined, the positive rate was 90.5%. The specificity was 77.9% with CA153, 77.9% with CA153 and CEA, 71.9% with CA153 and TPA, and 73.4% with all the three markers combined. Conclusion: The positive rate was increased remarkably with combined detection of CA153, CEA and TPA, however the specificity was not much changed, so the combined detection was valuable for differential diagnosis. (authors)

Assessment of CA 15.3, CEA and TPA concentrations during monitoring of breast cancer

DEFF Research Database (Denmark)

Sölétormos, G; Petersen, P H; Dombernowsky, P

2000-01-01

The variability of the tumor markers cancer antigen (CA) 15.3, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) during steady state concentrations and the rate of increase during progression is described. One hundred and ninety-two patients were monitored during first...... with above cutoff level values. Clinical and marker progression was registered for 75 (CA 15.3), 62 (CEA), and 57 (TPA) patients. The coefficients of total variation of steady state concentrations (comprising the intra- and interassay analytical imprecision and the within subject biological variation) were...... for TPA (0.0346). Our data indicate that criteria for assessment of sequential tumor marker concentrations should consider the marker in question, the steady state variability, the cutoff value, and the rate of increase during disease progression....

Catheter-directed Thrombolysis with Argatroban and tPA for Massive Iliac and Femoropopliteal Vein Thrombosis

Energy Technology Data Exchange (ETDEWEB)

Sharifi, Mohsen, E-mail: seyedmohsensharifi@yahoo.com [Arizona Cardiovascular Consultants (United States); Bay, Curt [A. T. Still University (United States); Nowroozi, Sasan; Bentz, Suzanne; Valeros, Gayle; Memari, Sara [Arizona Cardiovascular Consultants (United States)

2013-12-15

Purpose: Catheter-directed thrombolysis (CDT) is a highly effective approach in the treatment of deep venous thrombosis (DVT). There are no data on the primary use of CDT with argatroban and tissue plasminogen activator (tPA) in patients without heparin-induced thrombocytopenia (HIT). The aim of this study was to evaluate the efficacy and safety of the combined administration of argatroban and tPA during CDT for massive DVT in patients without HIT. Methods: Thirty-three patients with massive symptomatic iliac and femoropopliteal DVT underwent CDT with tPA and argatroban within 28 {+-} 6 h of presentation. The dose of tPA was 0.75-1 mg/h through the infusion port and that of argatroban at 0.3-1 {mu}g/kg/min through the side port of the sheath. The patients were evaluated for the efficacy and safety of CDT and recurrent symptomatic venous thromboembolism (VTE) at a mean follow-up of 22 months. Results: There was no bleeding or iatrogenic pulmonary embolism with the CDT regimen we used. Grade III lysis (complete resolution of thrombus on venography) was achieved in 30 patients (91 %). In 3 patients with additional inferior vena cava filter thrombosis, further thrombectomy of the filter was required. No patient developed recurrent VTE. Conclusion: Concomitant administration of argatroban and tPA is a highly safe and effective regimen for CDT for massive DVT.

Size- and Wavelength-Dependent Two-Photon Absorption Cross-Section of CsPbBr3 Perovskite Quantum Dots.

Science.gov (United States)

Chen, Junsheng; Žídek, Karel; Chábera, Pavel; Liu, Dongzhou; Cheng, Pengfei; Nuuttila, Lauri; Al-Marri, Mohammed J; Lehtivuori, Heli; Messing, Maria E; Han, Keli; Zheng, Kaibo; Pullerits, Tõnu

2017-05-18

All-inorganic colloidal perovskite quantum dots (QDs) based on cesium, lead, and halide have recently emerged as promising light emitting materials. CsPbBr 3 QDs have also been demonstrated as stable two-photon-pumped lasing medium. However, the reported two photon absorption (TPA) cross sections for these QDs differ by an order of magnitude. Here we present an in-depth study of the TPA properties of CsPbBr 3 QDs with mean size ranging from 4.6 to 11.4 nm. By using femtosecond transient absorption (TA) spectroscopy we found that TPA cross section is proportional to the linear one photon absorption. The TPA cross section follows a power law dependence on QDs size with exponent 3.3 ± 0.2. The empirically obtained power-law dependence suggests that the TPA process through a virtual state populates exciton band states. The revealed power-law dependence and the understanding of TPA process are important for developing high performance nonlinear optical devices based on CsPbBr 3 nanocrystals.

Preclinical assessment of adjunctive tPA and DNase for peritoneal dialysis associated peritonitis.

Directory of Open Access Journals (Sweden)

Amanda L McGuire

Full Text Available A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.

Unstandardized Responses to a "Standardized" Test: The edTPA as Gatekeeper and Curriculum Change Agent

Science.gov (United States)

Ledwell, Katherine; Oyler, Celia

2016-01-01

We examine edTPA (a teacher performance assessment) implementation at one private university during the first year that our state required this exam for initial teaching certification. Using data from semi-structured interviews with 19 teacher educators from 12 programs as well as public information on edTPA pass rates, we explore whether the…

TPA device for demonstration

International Nuclear Information System (INIS)

1980-02-01

The TPA (torus plasma for amature) is a small race-trac type device made by the technical service division to demonstrate basic properties of plasma such as electron temperature, conductivity, effect of helical field for toroidal drift, and shape of plasma in mirror and cusp magnetic field in linear section. The plasmas are produced by RF discharge (-500W) and/or DC discharge (-30 mA) within glass discharge tube. Where major radius is 50 cm, length of linear section is 50 cm, toroidal magnetic field is 200 gauss. The device has been designed to be compact with only 100 V power source (-3.2 KW for the case without helical field) and to be full automatic sequence of operation. (author)

Discovery and Evaluation of Anti-Fibrinolytic Plasmin Inhibitors Derived from 5-(4-Piperidyl)isoxazol-3-ol (4-PIOL)

DEFF Research Database (Denmark)

Schmidt, Thomas C.; Eriksson, Per-Olof; Gustafsson, David

2017-01-01

Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl...

Application of tumor markers SCC-Ag, CEA, and TPA in patients with cervical precancerous lesions.

Science.gov (United States)

Farzaneh, Farah; Shahghassempour, Shapour; Noshine, Bahram; Arab, Maliheh; Yaseri, Mehdi; Rafizadeh, Mitra; Alizadeh, Kamyab

2014-01-01

To determine the potential clinical utility of tumor markers CEA, TPA, and SCC-Ag for early detection of cervical precancerous lesions. A case-control study was carried out on 120 women (46 patients with histologically confirmed cervical precancerous lesions and 74 healthy controls). The significance of serum selected tumor markers in early detection of cervical intraepithelial neoplasia (CIN) were assessed. Of the case group, the rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to the manufacturer's cut-off values of 2 ng/ml, 5 ng/ml, and 70 U/ml for SCC-Ag, CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA and TPA tests could not distinguish between case and control groups. The diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag, 2.6 ng/ ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%, respectively. However, the area under the receiver operating characteristic curve was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA, respectively). Moreover, there was a highly significant direct correlation between SCC-Ag concentration and the degree of cervical precancerous lesions (r=0.847, ptumor marker in Iranian patients with CIN and it needs to be more evaluated by studies with larger populationa.

Association Between PAI-1 Activity Levels and t-PA Antigen with Glycemic Status in Prediabetic Population

Directory of Open Access Journals (Sweden)

Andi Fachruddin Benyamin

2016-11-01

Full Text Available Aim: to evaluate an association between fibrinolysis defect and glycemic status in prediabetic population by assessing the levels of t-PA antigen and PAI-1 activity. Methods: it was an observational study with cross-sectional approach. There were 72 subjects aged 30-50 years who had met the inclusion criteria. The diagnosis of diabetes mellitus (DM and glycemic index were determined based on the American Diabetes Association (ADA criteria. The PAI-1 and t-PA antigen levels were measured quantitatively using enzyme-linked immunosorbent assay (ELISA. Analysis between the levels of t-PA antigen and PAI-1 activity was performed using ANOVA. Results: the t-PA antigen level was significantly higher in subjects with impaired glucose tolerance (IGT and impaired fasting blood glucose (IFBG as well as subject with impaired fasting blood glucose (IFBG than those with normal glucose tolerance (NGT (p=0.047. The PAI-1 activity was significantly higher in subjects with IGT, IFBG and subjects with IFBG than NGT (p=0.024. There was a significant association between glycemic status in prediabetic subjects and PAI-1 activity (p=0.04. Conclusion: the level of t-PA antigen and PAI-1 activity were significantly higher in prediabetic subjects than those with NGT; and there was a significant association between glycemic status in prediabetic subjects and PAI-1 activity.

Copper Hugoniot measurements to 2.8 TPa on Z.

Energy Technology Data Exchange (ETDEWEB)

Furnish, Michael D.; Haill, Thomas A

2018-04-01

We conducted three Hugoniot and release experiments on copper on the Z machine at Hugoniot stress levels of 0.34 and 2.6 TPa, using two-layer copper/aluminum impactors travelling at 8 and 27 km/s and Z-quartz windows. Velocity histories were recorded for 4 samples of different thicknesses and 5 locations on the flyer plate (3 and 4 for the first two experiments). On-sample measurements provided Hugoniot points (via transit time) and partial release states (via Z-quartz wavespeed). Fabrication of the impactor required thick plating and several diamond-machining steps. The lower-pressure test was planned as a 2.5 TPa test, but a failure on the Z machine degraded its performance; however, these results corroborated earlier Cu data in the same stress region. The second test suffered from significant flyer plate bowing, but the third did not. The Hugoniot data are compared with the APtshuler/Nellis nuclear-driven data, other data from Z and elsewhere, and representative Sesame models.

ZEUS - standardized macros for the TPA computer

International Nuclear Information System (INIS)

Winde, M.

1976-01-01

An existing cross-assembler with macro-option was modified to allow the usage of the ZEUS macros. The ZEUS macros are understood by the assembler without prior definition by the user. ZEUS macros allow the programmer, who is obliged to code his TPA (PDP-8) programs on the assembler level to formulate his program logic as in a higher level language. ZEUS macros offer all basic elements necessary for structured programming. (author)

Effect of cesium salt of tungstophosphoric acid (Cs-TPA) on the properties of sulfonated polyether ether ketone (SPEEK) composite membranes for fuel cell applications

Energy Technology Data Exchange (ETDEWEB)

Dogan, Hacer; Inan, Tuelay Y.; Unveren, Elif [The Scientific and Technological Research Council of Turkey (TUeBiTAK), Marmara Research Center, Chemistry Institute, P.K. 21, 41470 Gebze-Kocaeli (Turkey); Kaya, Metin [DEMIRDOeKUeM A.S. 4 Eyluel Mah, ismet inoenue Cad. No:245 Bozueyuek/Bilecik (Turkey)

2010-08-15

We have prepared composite membranes for fuel cell applications. Cesium salt of tungstophosphoric acid (Cs-TPA) particles was synthesized by aqueous solutions of tungstophosphoric acid and cesium hydroxide and, Cs-TPA particles and sulfonated (polyether ether ketone) (SPEEK) with two sulfonation degrees (DS), 60 and 70%have been used. We examined both the effects of Cs-TPA in SPEEK membranes as functions of sulfonation degrees of SPEEK and the content of Cs-TPA. The performance of the composite membranes was evaluated in terms of water uptake, ion exchange capacity, proton conductivity, chemical stability, hydrolytic stability, thermal stability and methanol permeability. The morphology of the membranes was investigated with SEM micrographs. Increasing sulfonation degree of SPEEK from 60 to 70 caused agglomeration of the Cs-TPA particles. The methanol permeability was reduced to 4.7 x 10{sup -7} cm{sup 2}/s for SPEEK (DS: 60%)/Cs-TPA membrane with 10 wt.% Cs-TPA concentration, and acceptable proton conductivity of 1.3 x 10{sup -1} S/cm was achieved at 80 C under 100% RH. The weight loss at 900 C increased with the addition of inorganic particles, as expected. The hydrolytic stability of the SPEEK/Cs-TPA based composite membranes was improved with the incorporation of the Cs-TPA particles into the matrix. We also noted that SPEEK60/Cs-TPA composite membranes were hydrolytically more stable than SPEEK70/Cs-TPA composite membranes. On the other hand, Methanol, water vapor, and hydrogen permeability values of SPEEK60 composite membranes were found to be lower than that of Nafion {sup registered}. (author)

Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

International Nuclear Information System (INIS)

Fu, Wen; Gorodeski, George I; McCormick, Tom; Qi, Xiaoping; Luo, Liping; Zhou, Lingyin; Li, Xin; Wang, Bing-Cheng; Gibbons, Heidi E; Abdul-Karim, Fadi W

2009-01-01

The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X 7 receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X 7 system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X 7 action. Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X 7 -null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X 7 pore formation) were determined by confocal laser microscopy. (a) Co-application on the skin of the P2X 7 specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X 7 -receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X 7 receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the

Efficacy of DSP30-IL2/TPA for detection of cytogenetic abnormalities in chronic lymphocytic leukaemia/small lymphocytic lymphoma.

Science.gov (United States)

Holmes, P J; Peiper, S C; Uppal, G K; Gong, J Z; Wang, Z-X; Bajaj, R

2016-10-01

Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG-oligonucleotide DSP30/Interleukin-2 (IL-2) and DSP30/IL-2 in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA). We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013. In 2011, three cultures were set-up: unstimulated, DSP30/IL-2-stimulated and TPA-stimulated. In 2012-2013, two cultures were set-up: unstimulated and stimulated with TPA/DSP30/IL-2. In 2011, FISH had a detection rate of 91% and cytogenetics using DSP30/IL2 had a detection rate of 91% (n = 22). In 2012-2013, FISH had a detection rate of 79% and cytogenetics using TPA/DSP30/IL-2 had a detection rate of 98% (n = 40). The percentage of cases with normal FISH but abnormal cytogenetics increased from 9% in 2011 to 21% in 2012-2013. The TPA/DSP30/IL-2 cultures in 2012-2013 detected more novel abnormalities (n = 5) as compared to DSP30/IL-2 alone (n = 3). TPA/DSP30/IL2 was as good as or better than DSP30/IL2 alone. TPA/DSP30/IL-2 offers a high detection rate for CLL abnormalities with a single stimulated culture and may increase detection of clinically significant abnormalities. © 2016 John Wiley & Sons Ltd.

Management of acute ischemic stroke. What is the role of tPA and antithrombotic agents?

Science.gov (United States)

Meschia, J F

2000-05-15

Every patient with acute stroke who presents to a medical center that has appropriate resources should undergo evaluation for intravenous tPA therapy. Such therapy should not be given unless the patient meets strict eligibility criteria based on clinical, radiographic, and laboratory data. Intra-arterial thrombolysis may be a promising alternative to intravenous tPA therapy, but it should still be regarded as experimental. Daily aspirin therapy should be initiated immediately in most patients who do not receive intravenous tPA therapy and after 24 hours in most patients who receive this treatment. Measures should be taken to prevent medical complications, such as aspiration pneumonia, deep vein thrombosis, contractures, and pressure sores. Early initiation of rehabilitation can maximize stroke recovery. Whenever feasible, institutions should have stroke teams or units to streamline care and provide expertise for patients with acute stroke.

Luminoimmunometric Assay of Tissue Polypeptide Antigen (Tpa and Cancer Antigen 125 (Ca-125 in Breast Cancer Patients

Directory of Open Access Journals (Sweden)

O. El-Ahmady

1993-01-01

Full Text Available Serum TPA and CA-125 were determined in 86 individuals (66 with breast cancer representing the different stages and grades of the disease and 20 normal healthy controls. TPA and CA-125 were estimated using the L1A reagents supplied by BYK Sangtec. TPA showed sensitivity rates of 31.8%, 42.4% and 51.5% while CA-125 showed sensitivities of 16.3%, 18.6% and 25.6% at specificity levels of 100%, 95% and 90% respectively. Combined determination of the two markers resulted in some improvement in sensitivity. For follow-up of breast cancer patients after surgery both markers were of value and showed near-identical patterns.

Electric gun: a new method for generating shock pressures in excess of 1 TPa

International Nuclear Information System (INIS)

Steinberg, D.; Chau, H.; Dittbenner, G.; Weingart, R.

1978-01-01

By combining the electrically-driven, flying-plate, high-explosive initiator with well-known gas-gun technology, a novel method of generating and measuring shock pressures greater than 1 TPa has been developed. Called the electric gun, this system is competitive with laser or nuclear-driven, shock-wave, equation-of-state experiments in the 1 to 5 TPa range. Compared to those other methods, it has the advantage of simplicity, high precision, and low cost. In addition, its small size and low total energy allow it to be easily contained for experiments with toxic materials

IDENTIFIKASI PERTAMBAHAN PERSEBARAN LIMBAH TEMPAT PEMBUANGAN AKHIR (TPA JATIBARANG TAHUN 2015 MENGGUNAKAN METODE GEOLISTRIK

Directory of Open Access Journals (Sweden)

R S Wulandari

2016-04-01

Full Text Available Pada tahun 2000 timbunan sampah pada TPA Jatibarang yang berlokasi di Kelurahan Kedungpane Kecamatan Mijen Kota Semarang, sudah melebihi daya tampung yaitu sekitar 1,6 juta m3. Kondisi tersebut sangat berpotensi menimbulkan pencemaran lingkungan terutama pencemaran leacheat (air lindi. Oleh karena itu, dilakukan penelitian untuk mengetahui tingkat pencemaran limbah di daerah sekitar TPA Jatibarang pada tahun  2015 dengan menggunakan metode geolistrik konfigurasi schlumberger. Pengambilan data dilakukan pada tiga titik penelitian, dua berada didalam TPA dan satu berada di daerah perumahan sekitar TPA dengan panjang lintasan masing-masing 75 m. Pengolahan data hasil penelitian dilakukan dengan menggunakan softwareres2dinv. Hasil yang didapatkan berupa kondisi topografi serta nilai resistivitas lindi sebesar 0,044-0,70 Ωm. Persebaran lindi pada tahun 2015 menuju ke daerah dengan elevasi rendah yang mengarah ke Sungai Kreo. Sedangkan persebaran lindi pada lokasi penelitian di Perumahan Bambankerep Kecamatan Ngaliyan Kota Semarang juga telah diidentifikasikan tercemar oleh air lindi yang diduga berasal TPA Jatibarang.In 2000, piles of garbage in the landfill is located in the Village Jatibarang Kedungpane Mijen District of Semarang, has exceeded the capacity of around 1.6 million m3. The condition is potentially causing environmental pollution, especially pollution leacheat (leachate. Therefore, to investigate the pollution level of waste in the area around the landfill Jatibarang 2015 using geoelectric method Schlumberger configuration. Data were collected at three points research, two are in the landfill and one is located in a residential area around the landfill with a path length of each- each 75 m. Data processing results of research conducted by using softwareres2dinv. Results obtained in the form of topography and leachate resistivity value of 0.044 Ωm- 0.70 Ωm. Distribution of leachate in 2015 heading to areas with low elevation that

Production and Purification of Monoclonal Antibody Against Tumor Marker of TPA

Directory of Open Access Journals (Sweden)

Seyyed Amir Abbas Ghodrat

2016-05-01

Full Text Available Considering the invasive nature of cancer cells, one of the most important and best indicator of them is the markers inside them. One of the most important markers that observed in some types of cancer cells in various parts of the body is the Cytokeratin. Tissue plasminogen activator antigen (TPA is a Cytokeratin composed of molecules with various molecular weights. The level of TPA serum as associated with cellular growth level and tumorization of cells. In this research, the hybrid of spleen cells in BALB/c female mouse with myeloma cells was conducted with a ratio of 10:1. The resulting monoclonal antibodies were confirmed by SDS-PAGE and western blot. Protein G chromatography was utilized to purify monoclonal antibodies. The results for determining isotypes showed IgM and IgG classes. The titer of the antibody obtained from various clones was capable of identifying Cytokeratin antigen with a dilution of 1/10000. The resulting antibodies were finally confirmed by western blot and all the 5 resulting monoclonal antibodies were capable of identifying a 48 kDa protein. The results indicate that with the help of TPA marker and the monoclonal antibodies produced against them, this marker can be recognized quickly with great accuracy in suspicious cases of cancer. Thus, appropriate measures will be taken to prevent and fight off its probable side effects. This factor can be further used to build a diagonal kit with high sensitivity.

Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

NARCIS (Netherlands)

Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

2007-01-01

OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

Directory of Open Access Journals (Sweden)

Fu Wen

2009-04-01

Full Text Available Abstract Background The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X7 receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X7 system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X7 action. Methods Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X7-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA. Changes in cytosolic calcium or in ethidium bromide influx (P2X7 pore formation were determined by confocal laser microscopy. Results (a Co-application on the skin of the P2X7 specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28 the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b In the normal skin BzATP affected mainly P2X7-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d Levels of P2X7 receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for

The role of tumor markers (CEA, TPA, CA 19-9) in colon and rectum carcinomas

International Nuclear Information System (INIS)

Cangemi, V.; Volpino, P.; Fiori, E.; Giammarco, A.; Piat, G.

1987-01-01

We have evaluated the diagnostic efficacy (sensitivity, specificity, accuracy, predictive malignancy index) of CEA, TPA, CA 19-9 in colon and rectum tumors (56 cases), the difference in behaviour of these markers in relation to the stage and grading of the cancer, their reliability regarding postsurgical relapses and/or metastases. The sensitivity of CEA (>10 ng/ml), TPA (>130 U/L), CA 19-9 (>37 u/ml) for diagnostic purpose was rather limited (28.6% - 30% - 18.5%) with a malignancy prediction value of 100% - 81.8% - 62.5%. With regard to relapses and/or metastases, the diagnostic efficacy of the marker proved to be evident only for CEA, TPA, CA 19-9 value greater than 25 ng/ml, 250 U/L and 100 u/ml. The use of thethree markers together was certainly an advantage both for primitive tumors (sensitivity: 52.8%) and relapses and/or metastases after surgery (sensitivity: 66.7%)

Strain differences in mouse skin carcinogenesis experiments using ionizing radiation and the tumor promoter TPA

International Nuclear Information System (INIS)

Jaffe, D.R.; Bowden, G.T.

1985-01-01

Ionizing radiation has been shown to be a complete carcinogen in rodent skin when administered repeatedly. The initiating potential of ionizing radiation in mouse skin was tested in a classical two-stage protocol in both CD-1 and Sencar mice. Beta radiation (0.5, 1.5, 3.0 and 5.0 Gy) was administered by a strontium 90 applicator followed two weeks later by twice weekly application of 5 μg TPA. A statistical difference in the papilloma incidence between radiation initiated, TPA promoted versus non-initiated TPA promoted groups was not found (25-35% animals with papillomas and 0.35-0.45 papillomas per mouse at 65 weeks of promotion for both initiated and non-initiated mice). There appeared to be no strain differences between the CD-1 and Sencar in response to the initiating effects if ionizing radiation. This is in direct contrast to the studies showing Sencar mice to be much more sensitive than CD-1 to the initiating effects of chemical carcinogens

RBC-coupled tPA prevents cerebrovasodilatory impairment and tissue injury in pediatric cerebral hypoxia/ischemia through inhibition of ERK MAPK unregulation

Energy Technology Data Exchange (ETDEWEB)

Ganguly, Kumkum [Los Alamos National Laboratory; Armstead, William M [U PENNSYLVANIA; Kiessling, J W [U PENNSYLVANIA; Chen, Xiao - Han [U PENNSYLVANIA; Smith, Douglas H [U PENNSYLVANA; Higazi, Abd Ar [U PENNSYLVANIA; Cines, Douglas B [U PENNSYLVANIA; Bdeir, Khalil [U PENNSYLVANIA; Zaitsev, Sergei [U PENNSYLVANIA; Muzykantov, Vladimir R [U PENNSYLVANIA

2008-01-01

Babies experience hypoxia (H) and ischemia (I) from stroke. The only approved treatment for stroke is fibrinolytic therapy with tissue-type plasminogen activator (tPA). However, tPA potentiates H/I-induced impairment of responses to cerebrovasodilators such as hypercapnia and hypotension, and blockade of tPA-mediated vasoactivity prevents this deleterious effect. Coupling tPA to RBCs reduces its CNS toxicity through spatially confining the drug to the vasculature. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, is upregulated after H/I. In this study we determined if RBC-tPA given before or after cerebral H/I would preserve responses to cerebrovasodilators and prevent neuronal injury mediated through the ERK MAPK pathway. Animals given RBC-tPA maintained responses to cerebrovasodilators at levels equivalent to pre-H/I values. CSF and brain parenchymal ERK MAPK was elevated by H/I and this upregulation was potentiated by tPA, but blunted by RBC-tPA. U 0126, an ERK MAPK antagonist, also maintained cerebrovasodilation post H/I. Neuronal degeneration in CA1 hippocampus and parietal cortex after H/I was exacerbated by tPA, but ameliorated by RBC-tPA and U 0126. These data suggest that coupling tPA to RBCs may offer a novel approach towards increasing the benefit/risk ratio of thrombolytic therapy for CNS disorders associated with H/I.

MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae.

Science.gov (United States)

Jarocki, Veronica M; Santos, Jerran; Tacchi, Jessica L; Raymond, Benjamin B A; Deutscher, Ania T; Jenkins, Cheryl; Padula, Matthew P; Djordjevic, Steven P

2015-01-01

Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae.

The effect of local sustained delivery of sirolimus on the vascular PAI-1 and t-PA expression after angioplasty

International Nuclear Information System (INIS)

E Yajun; He Nengshu; Fan Hailun

2011-01-01

Objective: To investigate the effect of local sustained delivery of sirolimus on the vascular inhibitor of plasminogen activator-1 (PAI-1) and tissue type plasminogen activator (t-PA) expression after angioplasty. Methods: Experimental common carotid artery injury model was established in the rats. A total of 30 male Wistar rats were divided into experimental group (n=20) and control group (n=10). Adventitial administration of drug was applied. Pluronic F-127 gel containing sirolimus was administered to the exposed adventitial surface of injured carotid artery. The experimental group was divided into high concentration (600 μg/100 μl) sub-group and low concentration (300 μg/100μl) sub-group according to the concentration of sirolimus delivered. The effect of local sustained delivery sirolimus on vascular PAI-1 and t-PA expression after percutaneous angioplasty was evaluated by immunohistochemistry. Results: Compared to control group, 15 and 30 days after injury local sustained delivery of sirolimus in both high concentration and low concentration sub-groups the expression of the PAI-1 in neointima was significantly enhanced (P 0.05). At 15 and 30 days after injury, the expression of t-PA in neointima was decreased in both high and low concentration sub-groups (P<0.05), and the expression of t-PA in media was significantly decreased in high concentration sub-group (P<0.05) while on significant difference could be detected in low concentration sub-group. Conclusion: Local sustained delivery of sirolimus can induce the high expression of PAI-1 and low expression of t-PA in neointima although it inhibits the proliferation of neointima in the same time, and the imbalanced expression of t-PA and PAI-1 may probably play an important role in the late formation of thrombosis after the placement of drug-eluting stent. (authors)

tPA variant tPA-A296-299 Prevents impairment of cerebral autoregulation and necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET-1.

Science.gov (United States)

Armstead, William M; Hekierski, Hugh; Yarovoi, Serge; Higazi, Abd Al-Roof; Cines, Douglas B

2018-01-01

Tissue-type plasminogen activator (tPA) is neurotoxic and exacerbates uncoupling of cerebral blood flow (CBF) and metabolism after stroke, yet it remains the sole FDA-approved drug for treatment of ischemic stroke. Upregulation of c-Jun-terminal kinase (JNK) after stroke contributes to tPA-mediated impairment of autoregulation, but the role of endothelin-1 (ET-1) is unknown. Based on the Glasgow Coma Scale, impaired autoregulation is linked to adverse outcomes after TBI, but correlation with hippocampal histopathology after stroke has not been established. We propose that given after stroke, tPA activates N-Methyl-D-Aspartate receptors (NMDA-Rs) and upregulates ET-1 in a JNK dependent manner, imparing autoregulation and leading to histopathology. After stroke, CBF was reduced in the hippocampus and reduced further during hypotension, which did not occur in hypotensive sham pigs, indicating impairment of autoregulation. Autoregulation and necrosis of hippocampal CA1 and CA3 neurons were further impaired by tPA, but were preserved by the ET-1 antagonist BQ 123 and tPA-A, 296-299 a variant that is fibrinolytic but does not bind to NMDA-Rs. Expression of ET-1 was increased by stroke and potentiated by tPA but returned to sham levels by tPA-A 296-299 and the JNK antagonist SP600125. Results show that JNK releases ET-1 after stroke. Tissue-type plasminogen activator -A 296-299 prevents impairment of cerebral autoregulation and histopathology after stroke by inhibiting upregulation of ET-1. © 2017 Wiley Periodicals, Inc.

Photovoltaic Small Molecules of TPA(FxBT-T-Cz)3: Tuning Open-Circuit Voltage over 1.0 V for Their Organic Solar Cells by Increasing Fluorine Substitution.

Science.gov (United States)

Wang, Qiong; Duan, Linrui; Tao, Qiang; Peng, Wenhong; Chen, Jianhua; Tan, Hua; Yang, Renqiang; Zhu, Weiguo

2016-11-09

To simultaneously improve both open-circuit voltage (V oc ) and short-circuit current density (J sc ) for organic solar cells, a novel D(A-π-Ar) 3 type of photovoltaic small molecules of TPA(F x BT-T-3Cz) 3 was designed and synthesized, which contain central triphenylamine (TPA), terminal carbazole (Cz), armed fluorine-substituted benzothiadiazole (F x BT, where x = 1 or 2), and bridged thiophene (T) units. A narrowed ultraviolet-visible absorption and a decreasing highest occupied molecular orbital energy level were observed from TPA(F 1 BT-T-3Cz) 3 to TPA(F 2 BT-T-3Cz) 3 with increasing fluorine substitution. However, the TPA(F 2 BT-T-3Cz) 3 /PC 71 BM-based solar devices showed a rising V oc of 1.01 V and an enhanced J sc of 10.84 mA cm -2 as well as a comparable power conversion efficiency of 4.81% in comparison to the TPA(F 1 BT-T-3Cz) 3 /PC 71 BM-based devices. Furthermore, in comparison to the parent TPA(BT-T-3Cz) 3 molecule without fluorine substitution, the fluorine-substituted TPA(F x BT-T-3Cz) 3 molecules exhibited significantly incremental V oc and J sc values in their bulk heterojunction organic solar cells, owing to fluorine incorporation in the electron-deficient benzothiadiazole unit.

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2.

Science.gov (United States)

Li, Qun; Laumonnier, Yves; Syrovets, Tatiana; Simmet, Thomas

2011-11-01

To identify proteins that interact with the C-terminal fragment of annexin A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a heterotetramer (AA2t) containing annexin A2. The gene that encodes the A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes, and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was determined using Western blot analysis. The identification of proteins that interact with A2IC and are encoded in a human monocyte cDNA library was performed using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction kit. Nucleotide sequence databases were searched for homologous sequences using BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was conducted using a small-scale yeast transformation and X-gal assay. The yeast transformed with plasmids encoding the bait proteins were screened with a human monocyte cDNA library by reconstituting full-length transcription factors containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid approach. After screening 1×10(7) clones, 23 independent β-Gal-positive clones were identified. Sequence analysis and a database search revealed that 15 of these positive clones matched eight different proteins (SNX17, ProCathepsin S, RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact with annexin A2). A2IC A2IC interacts with various proteins to form protein complexes, which may contribute to the molecular mechanism of monocyte activation induced by plasmin. The yeast two-hybrid system is an efficient approach for investigating protein interactions.

Penurunan Logam Timbal (Pb pada Limbah Cair TPA Piyungan Yogyakarta dengan Constructed Wetlands Menggunakan Tumbuhan Eceng Gondok (Eichornia Crassipes

Directory of Open Access Journals (Sweden)

Eko Siswoyo

2015-10-01

Full Text Available Salah satu permasalahan lingkungan yang ditimbulkan dari adanya lindi di TPA Piyungan yaitu pencemaran pada badan air, sungai dan air tanah. Untuk mengatasi permasalahan ini salah satunya dengan sistem Constructed Wetlands dengan menggunakan tumbuhah eceng gondok. Tujuan dari penelitian ini adalah untuk mengetahui tingkat penurunan konsentrasi Timbal (Pb yang terdapat dalam limbah cair TPA Piyungan dengan Constructed Wetlands menggunakan tumbuhan eceng gondok dan untuk mengetahui seberapa besar kapasitas serapan tumbuhan eceng gondok terhadap kandungan Timbal (Pb dalam limbah cair TPA Piyungan.Dalam penelitian ini digunakan reaktor yang terbuat dari kayu yang dilapisi plastik dengan ukuran 0,5 m x 1,0 m. Setiap reaktor diberi media tanah 5 cm, dan diberi tumbuhan sebanyak 14 buah. Reaktor tersebut diberi perlakuan dengan konsentrasi limbah yang bervariasi (100%, 75%, 50%, 25%, dan 0%, dan waktu pengambilan sampel (0, 3, 6, 9, 12 hari. Dengan menggunakan metode SSA (Spektrofotometri Serapan Atom.Berdasarkan pengujian diperoleh bahwa penurunan logam Pb pada limbah cair TPA Piyungan hari ke- 12, yaitu sebesar 0.0501mg/L pada konsentrasi 100%, 0.0295mg/L pada konsentrasi 75%, 0.0267mg/L pada konsentrasi 50% dan 0.0041 mg/L pada konsentrasi 25%.

t-PA power-pulse spray with rheolytic mechanical thrombectomy using cross-sectional image-guided portal vein access for single setting treatment of subacute superior mesenteric vein thrombosis.

Science.gov (United States)

Syed, Mubin I; Gallagher, Ryan M; Ahmed, Rukan S; Shaikh, Azim; Roberto, Edward; Patel, Sumeet

2018-01-01

Isolated superior mesenteric vein (SMV) thrombosis is a rare but potentially fatal condition if untreated. Current treatments include transjugular or transhepatic approaches for rheolytic mechanical thrombectomy and subsequent infusions of thrombolytics. Tissue plasminogen activator (t-PA) power-pulse spray can provide benefit in a single setting without thrombolytic infusions. Computed tomography (CT) guidance for portal vein access is underutilized in this setting. Case 1 discusses acute SMV thrombosis treated with rheolytic mechanical thrombectomy alone using ultrasound guidance for portal vein access. Case 2 discusses subacute SMV thrombosis treated with the addition of t-PA power-pulse spray to the rheolytic mechanical thrombectomy, using CT guidance for portal vein access. With rheolytic mechanical thrombectomy alone, the patient in Case 1 had significant improvement in abdominal pain. Follow-up CT demonstrated no residual SMV thrombosis and the patient continued to do well in long-term follow-up. With the addition of t-PA power-pulse spray to rheolytic mechanical thrombectomy, the patient in Case 2 with subacute SMV thrombosis dramatically improved postprocedure with resolution of abdominal pain. Follow-up imaging demonstrated patency to the SMV and partial resolution of thrombus. The patient continued to do well at 2-year follow-up. Adding t-PA power-pulse spray to rheolytic mechanical thrombectomy can provide benefit in a single setting versus mechanical thrombectomy alone and prevent the need for subsequent infusions of thrombolytic therapy. CT guidance is a useful alternative of localization for portal vein access via the transhepatic route that is nonoperator-dependent and helpful in the case of obese patients.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) accelerates expression of differentiation markers in cultures of rat palatal epithelial cells

DEFF Research Database (Denmark)

Arenholt, D; Dabelsteen, Erik

1987-01-01

Cultures of rat palatal epithelium grown on collagen rafts were treated with different doses of the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Sections from biopsies taken 1, 6, 24, and 48 hr after the addition of TPA were examined for the localization of staining by blood ...

Plasminogen Binding Proteins and Plasmin Generation on the Surface of Leptospira spp.: The Contribution to the Bacteria-Host Interactions

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Monica L. Vieira

2012-01-01

Full Text Available Leptospirosis is considered a neglected infectious disease of human and veterinary concern. Although extensive investigations on host-pathogen interactions have been pursued by several research groups, mechanisms of infection, invasion and persistence of pathogenic Leptospira spp. remain to be elucidated. We have reported the ability of leptospires to bind human plasminogen (PLG and to generate enzimatically active plasmin (PLA on the bacteria surface. PLA-coated Leptospira can degrade immobilized ECM molecules, an activity with implications in host tissue penetration. Moreover, we have identified and characterized several proteins that may act as PLG-binding receptors, each of them competent to generate active plasmin. The PLA activity associated to the outer surface of Leptospira could hamper the host immune attack by conferring the bacteria some benefit during infection. The PLA-coated leptospires obstruct complement C3b and IgG depositions on the bacterial surface, most probably through degradation. The decrease of leptospiral opsonization might be an important aspect of the immune evasion strategy. We believe that the presence of PLA on the leptospiral surface may (i facilitate host tissue penetration, (ii help the bacteria to evade the immune system and, as a consequence, (iii permit Leptospira to reach secondary sites of infection.

From fibrinolysis to the plasminogen-plasmin system and beyond: a remarkable growth of knowledge, with personal observations on the history of fibrinolysis.

Science.gov (United States)

Kwaan, Hau C

2014-07-01

Great advances have been made in our understanding of the fibrinolytic system from the initial discovery of proteolysis of fibrin by plasmin to the multifaceted and complex role of the plasminogen-plasmin (P-P) system. We now know that the P-P system is composed of several serine proteases and their inhibitors (serpins). This system is involved in many physiological functions, including embryogenesis, cell migration, and wound healing. They also play an important role in the pathogenesis of many diseases, including atherosclerosis, obesity, cancer, and even autoimmune disorders, and neuronal degeneration. Knowledge of their role in cancer enables their use as a prognostic factor. Therapeutic use of various forms of proteases derived from this system has been employed as thrombolytic agents. In addition, small molecules designed to inhibit many of the components of the P-P system are now available for clinical trial, aimed at treatment of these various disorders. The history of such remarkable development of our knowledge on fibrinolysis is reviewed in this article. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Comparison of altered expression of histocompatibility antigens with altered immune function in murine spleen cells treated with ultraviolet radiation and/or TPA

International Nuclear Information System (INIS)

Pretell, J.O.; Cone, R.E.

1985-01-01

Previous studies in our laboratory demonstrated that several treatments that inhibited the ability of cells to stimulate the mixed lymphocyte reaction (MLR) also blocked the shedding of histocompatibility antigens and Ia antigens from murine spleen cells. In the present studies, one of these treatments, ultraviolet radiation (UV), was shown to cause an initial loss in the density of H-2K, IA, and IE antigens prior to the block in shedding observed after culture of these cells. Further analysis revealed that the UV-induced loss of antigens could be prevented by the presence of colchicine during irradiation. Biosynthetic analyses revealed the IA antigen synthesis was also inhibited in the UV-irradiated cells. Examination of the effects of a second agent, 12-0-tetradecanoylphorbol-13-acetate (TPA) on the turnover of histocompatibility antigens revealed that the biosynthesis and shedding of these antigens were accelerated by this agent. However, addition of TPA to UV-irradiated cells did not result in a reversal of the UV-induced block in biosynthesis of IA antigens. Results of immune function assays correlated with the biochemical studies: UV-irradiation inhibited the generation of the MLR, but TPA enhanced this reaction, and addition of TPA to mixed lymphocyte cultures with UV-irradiated stimulators did not reverse the UV-induced inhibition. These results suggest that, although the turnover of histocompatibility antigens may be affected by TPA and UV in an antagonistic fashion, additional factors other than the expression of histocompatibility antigens are operating in the inhibition of stimulation of an MLR by UV radiation or its enhancement by TPA

The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

Science.gov (United States)

Živković, Maja; Starčević Čizmarević, Nada; Lovrečić, Luca; Klupka-Sarić, Inge; Stanković, Aleksandra; Gašparović, Iva; Dinčić, Evica; Stojković, Ljiljana; Rudolf, Gorazd; Šega Jazbec, Saša; Perković, Olivio; Sinanović, Osman; Sepčić, Juraj; Kapović, Miljenko; Peterlin, Borut

2014-01-01

Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P = 0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P = 0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P = 0.017). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS. PMID:24825926

Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8 induction in lung epithelial cells

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Refsnes M

2014-12-01

Full Text Available Magne Refsnes, Tonje Skuland, Marit Låg, Per E Schwarze, Johan Øvrevik Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway Abstract: Different toxic agents have a varying potential to induce the production of the proinflammatory chemokine, CXCL8 (interleukin [IL]-8, in lung cells. A critical question is which mechanisms determine the magnitude and persistence of the CXCL8 responses to different stimuli. To approach this, we compared the potential of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA, and sodium fluoride (NaF to induce CXCL8 responses in A549 cells, with emphasis on the importance of nuclear factor kappa B (NF-κB- and mitogen-activated protein kinase (MAPK signaling. Notably, TPA induced a greater release of CXCL8 than did NaF. Furthermore, TPA induced a strong, rapid, but transient upregulation of CXCL8 messenger (mRNA, whereas NaF induced a weaker, more delayed, but persistent upregulation. With respect to signaling, TPA led to an early, strong, and relatively transient extracellular signal-regulated kinase (ERK1/2 phosphorylation, and a less marked and even more transient phosphorylation of c-jun-N-terminal kinases (JNK1/2 and p38. In contrast, NaF elicited a lower, but relatively sustained increase in phosphorylation of ERK1/2, and a marked phosphorylation of p38 and JNK1/2, with the JNK1/2 response as most transient. Only ERK1/2 inhibition affected the TPA response, whereas inhibition of all the three MAPK cascades reduced NaF-induced CXCL8 release. TPA also induced an early, marked phosphorylation/translocation of p65 (NF-κB, whereas NaF induced slower, less pronounced effects on p65. The CXCL8 responses by TPA and NaF were reduced by p65-siRNA. In conclusion, all MAPK cascades were involved in NaF-induced CXCL8 release, whereas only ERK1/2 activation was involved in response to TPA. Furthermore, NF-κB activation appeared to be

UV laser-driven shock-wave experiments at ultrahigh-pressures up to 5 TPa

Energy Technology Data Exchange (ETDEWEB)

Cottet, F.; Hallouin, M.; Romain, J.P. (GRECO ILM, Laboratoire d' Enegetique et Detonique, ENSMA, 86 - Poitiers (France)); Fabbro, R.; Faral, B. (GRECO ILM, Laboratoire de Physique des Milieux Ionises, Ecole Polytechnique, 91 - Palaiseau (France))

1984-11-01

Laser-driven shock pressures up to 5 TPa at 0.26 ..mu..m wavelenth have been evaluated from measurements of shock velocity through thin metallic foils (Al, Au, Cu) by streak camera records of shock luminosity at the near face of the foil.

UV laser-driven shock-wave experiments at ultrahigh-pressures up to 5 TPa

International Nuclear Information System (INIS)

Cottet, F.; Hallouin, M.; Romain, J.P.; Fabbro, R.; Faral, B.

1984-01-01

Laser-driven shock pressures up to 5 TPa at 0.26 μm wavelenth have been evaluated from measurements of shock velocity through thin metallic foils (Al, Au, Cu) by streak camera records of shock luminosity at the near face of the foil

Plasminogen deficiency causes reduced corticospinal axonal plasticity and functional recovery after stroke in mice.

Directory of Open Access Journals (Sweden)

Zhongwu Liu

Full Text Available Tissue plasminogen activator (tPA has been implicated in neurite outgrowth and neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg into plasmin. In this study, using plasminogen knockout (Plg-/- mice and their Plg-native littermates (Plg+/+, we investigated the role of Plg in axonal remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n = 10/group were subjected to permanent intraluminal monofilament middle cerebral artery occlusion (MCAo. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA was injected into the left motor cortex to anterogradely label the corticospinal tract (CST. Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In Plg+/+ mice, the motor functional deficiency after stroke progressively recovered with time. In contrast, recovery in Plg-/- mice was significantly impaired compared to Plg+/+ mice (p0.82, p<0.01. Plg-/- neurons exhibited significantly reduced neurite outgrowth. Our data suggest that plasminogen-dependent proteolysis has a beneficial effect during neurological recovery after stroke, at least in part, by promoting axonal remodeling in the denervated spinal cord.

Temperature dependence of the two photon absorption in indium arsenide

International Nuclear Information System (INIS)

Berryman, K.W.; Rella, C.W.

1995-01-01

Nonlinear optical processes in semiconductors have long been a source of interesting physics. Two photon absorption (TPA) is one such process, in which two photons provide the energy for the creation of an electron-hole pair. Researchers at other FEL centers have studied room temperature TPA in InSb, InAs, and HgCdTe. Working at the Stanford Picosecond FEL Center, we have extended and refined this work by measuring the temperature dependence of the TPA coefficient in InAs over the range from 80 to 350 K at four wavelengths: 4.5, 5.06, 6.01, and 6.3 microns. The measurements validate the functional dependence of recent band structure calculations with enough precision to discriminate parabolic from non-parabolic models, and to begin to observe smaller effects, such as contributions due to the split-off band. These experiments therefore serve as a strong independent test of the Kane band theory, as well as providing a starting point for detailed observations of other nonlinear absorption mechanisms

Functional role of proteolytic cleavage at arginine-275 of human tissue plasminogen activator as assessed by site-directed mutagenesis

International Nuclear Information System (INIS)

Tate, K.M.; Higgins, D.L.; Holmes, W.E.; Winkler, M.E.; Heyneker, H.L.; Vehar, G.A.

1987-01-01

Activation of the zymogen form of a serine protease is associated with a conformational change that follows proteolysis at a specific site. Tissue-type plasminogen activator (t-PA) is homologous to mammalian serine proteases and contains an apparent activation cleavage site at arginine-275. To clarify the functional consequences of cleavage at arginine-275 of t-PA, site-specific mutagenesis was performed to convert arginine-275 to a glutamic acid. The mutant enzyme (designated Arg-275 → Glu t-PA) could be converted to the two-chain form by Staphylococcus aureus V8 protease but not by plasmin. The one-chain form was 8 times less active against the tripeptide substrate H-D-isoleucyl-L-prolyl-L-arginine-rho-nitroanilide (S-2288), and the ability of the enzyme to activate plasminogen in the absence of fibrinogen was reduced 20-50 times compared to the two-chain form. In contrast, one-chain Arg-275 → Glu t-PA has equal activity to the two-chain form when assayed in the presence of physiological levels of fibrinogen and plasminogen. Fibrin bound significantly more of the one-chain form of t-PA than the two-chain form for both the wild-type and mutated enzymes. One- and two-chain forms of the wild-type and mutated plasminogen activators slowly formed complexes with plasma protease inhibitors, although the one-chain forms showed decreased complex formation with → 2 -macroglobulin. The one-chain form of t-PA therefore is fully functional under physiologic conditions and has a increased fibrin binding compared to the two-chain form

t-PA power-pulse spray with rheolytic mechanical thrombectomy using cross-sectional image-guided portal vein access for single setting treatment of subacute superior mesenteric vein thrombosis

Directory of Open Access Journals (Sweden)

Mubin I Syed

2018-01-01

Full Text Available Background: Isolated superior mesenteric vein (SMV thrombosis is a rare but potentially fatal condition if untreated. Current treatments include transjugular or transhepatic approaches for rheolytic mechanical thrombectomy and subsequent infusions of thrombolytics. Tissue plasminogen activator (t-PA power-pulse spray can provide benefit in a single setting without thrombolytic infusions. Computed tomography (CT guidance for portal vein access is underutilized in this setting. Materials and Methods: Case 1 discusses acute SMV thrombosis treated with rheolytic mechanical thrombectomy alone using ultrasound guidance for portal vein access. Case 2 discusses subacute SMV thrombosis treated with the addition of t-PA power-pulse spray to the rheolytic mechanical thrombectomy, using CT guidance for portal vein access. Results: With rheolytic mechanical thrombectomy alone, the patient in Case 1 had significant improvement in abdominal pain. Follow-up CT demonstrated no residual SMV thrombosis and the patient continued to do well in long-term follow-up. With the addition of t-PA power-pulse spray to rheolytic mechanical thrombectomy, the patient in Case 2 with subacute SMV thrombosis dramatically improved postprocedure with resolution of abdominal pain. Follow-up imaging demonstrated patency to the SMV and partial resolution of thrombus. The patient continued to do well at 2-year follow-up. Conclusions: Adding t-PA power-pulse spray to rheolytic mechanical thrombectomy can provide benefit in a single setting versus mechanical thrombectomy alone and prevent the need for subsequent infusions of thrombolytic therapy. CT guidance is a useful alternative of localization for portal vein access via the transhepatic route that is nonoperator-dependent and helpful in the case of obese patients.

Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.

Science.gov (United States)

Fujita, M; Hong, K; Ito, Y; Fujii, R; Kariya, K; Nishimuro, S

1995-10-01

Nattokinase is a new fibrinolytic enzyme which cleaves directly cross-linked fibrin in vitro. In this study, we investigated the thrombolytic effect of nattokinase on a thrombus in the common carotid artery of rat in which the endothelial cells of the vessel wall were injured by acetic acid. When a section of occluded vessel was stained for CD61 antigen by immunofluorescence utilizing a monoclonal antibody, the antigen was localized around the surface of the occluded blood vessels. This result suggests that the occlusive thrombosis was caused by platelet aggregation. In addition, thrombolysis with urokinase (UK; 50000 IU/kg, i.v.) or tissue plasminogen activator (tPA; 13300 IU/kg, i.v.) in our model was observed to restore the blood flow over a 60 min monitoring period. The results indicate that our chemically induced model is useful for screening and evaluating a thrombolytic agent. We evaluated the thrombolytic activity of nattokinase using this model and compared it with fibrino(geno)lytic enzyme, plasmin or elastase. On a molar basis, the recovery of the arterial blood flow with nattokinase, plasmin and elastase were 62.0 +/- 5.3%, 15.8 +/- 0.7% and 0%, respectively. The results indicate that the thrombolytic activity of nattokinase is stronger than that of plasmin or elastase in vivo.

Next Generation Science Standards and edTPA: Evidence of Science and Engineering Practices

Science.gov (United States)

Brownstein, Erica M.; Horvath, Larry

2016-01-01

Science teacher educators in the United States are currently preparing future science teachers to effectively implement the "Next Generation Science Standards" (NGSS) and, in thirteen states, to successfully pass a content-specific high stakes teacher performance assessment, the edTPA. Science education and teacher performance assessment…

Prospects for generating 1-10 TPa pressures with a railgun

International Nuclear Information System (INIS)

Hawke, R.S.; Scudder, J.K.

1979-01-01

It has been demonstrated that a plasma arc can be accelerated along two current carrying parallel rails and used to accelerate a projectile. We have performed an extensive analysis and found the task of using a railgun to accelerate an impactor plate to velocities of 10 to 40 km/s to be feasible with contemporary technology. This range of impact velocities would enable shock pressures of 1 to 10 TPa to be generated for EOS research

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

A curcumin-based TPA four-branched copper(II) complex probe for in vivo early tumor detection

Energy Technology Data Exchange (ETDEWEB)

Pi, Zongxin [Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei 230001 (China); Wang, Jiafeng; Jiang, Bo [Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038 (China); Cheng, Gang [Department of Chemical and Chemical Engineering, Hefei Normal University, Hefei 230001 (China); Zhou, Shuangsheng, E-mail: zshuangsheng@126.com [Department of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038 (China); Center of Modern Experimental Technology, Anhui University, Hefei 230038 (China)

2015-01-01

A multibranched Cu(II) complex CuL{sub 2} curcumin-based was synthesized and characterized by single-crystal X-ray diffraction analysis. The photophysical properties of the complex have been investigated both experimentally and theoretically. The results show that the target complex exhibits higher quantum yield and larger two-photon absorption (TPA) cross-section in the near infrared (NIR) region compared with its free ligand. The cell imaging studies in vitro and in vivo reveal that the complex shows good photostability and excellent tumor targeting capability to tested cancerous cells, which can be potentially used for early tumor detection. - Graphical abstract: A multibranched Cu(II) complex was prepared from curcumin. The photophysical properties of the obtained complex have been investigated. The results exhibit that the complex has high capability to test cancerous cells and can distinguish between the cancerous and noncancerous cells, which should be potentially used for early tumor detection. - Highlights: • A novel multi-branched copper complex was synthesized. • The obtained compounds exhibited obvious TPA in high polar solvents. • The complex is a low toxicity at low-micromolar concentrations. • The complex exhibits larger TPA cross-section and brighter TPF imaging. • The complex has excellent targeting capability to tested cancerous cells.

Kandungan Nitrat dan Fosfat Sedimen serta Keterkaitannya dengan Kerapatan Mangrove di Kawasan Mertasari di Aliran Sungai TPA Suwung Denpasar, Bali

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Ni Nyoman Desi Kusuma Dewi

2017-06-01

Full Text Available Mangrove is a green plants tolerant of salt water, which grows mainly along the sheltered coastal areas, especially along the bay or in estuaries. Final Disposal (TPA Rubbish Suwung which located in the village Pedungan South Denpasar District is the rubbish dumps originating from the city of Denpasar and Badung. There is a natural mangrove vegetation in the river TPA. Mertsari area which located in the village of Sanur, West Denpasar District is a mangrove planting area and tourism destination on the Mertasari Beach. The purpose of this research are as follows: (1 To identify the content of nitrate and phosphate in mangrove sediments, (2 To determine the density of mangrove in Region Mertasari and TPA Suwung River Flow and (3 To describe the mangrove density is linkage with nitrate and phosphate mangrove sediments. The method used on this research is linear regression. Nitrate and phosphate sediments of mangroves in TPA Suwung River Flow and Region Mertasari range of 0.04 ppm - 79.034 ppm. The average density results of the mangrove tree level, saplings and seedlings in different locations ranged 0.01 ind / m2 - 0.32 ind / m2. The river's flow TPA Suwung produce a simple linear regression calculation of nitrate mangrove sediments density y = -0,002x + 0,288 (R2 10,1 %, and the calculation of the density sedimentary  phosphate mangrove produce y = 0,007x + 0,125  (R2 6,1 %. The results of simple linear regression calculation of nitrate sediments density Mertasari mangrove area is y = -0,002x+ 0,537  R2 = 4,7%, and the calculation of the density sedimentary  phosphate mangrove produce y = -0,038x + 0,777 (R2 63,7 %.

Tissue-type plasminogen activator-binding RNA aptamers inhibiting low-density lipoprotein receptor family-mediated internalisation.

Science.gov (United States)

Bjerregaard, Nils; Bøtkjær, Kenneth A; Helsen, Nicky; Andreasen, Peter A; Dupont, Daniel M

2015-07-01

Recombinant tissue-type plasminogen activator (tPA, trade name Alteplase), currently the only drug approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of cerebral ischaemic stroke, has been implicated in a number of adverse effects reportedly mediated by interactions with the low-density lipoprotein (LDL) family receptors, including neuronal cell death and an increased risk of cerebral haemorrhage. The tissue-type plasminogen activator is the principal initiator of thrombolysis in human physiology, an effect that is mediated directly via localised activation of the plasmin zymogen plasminogen at the surface of fibrin clots in the vascular lumen. Here, we sought to identify a ligand to tPA capable of inhibiting the relevant LDL family receptors without interfering with the fibrinolytic activity of tPA. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to isolate tPA-binding RNA aptamers, which were characterised in biochemical assays of tPA association to low density lipoprotein receptor-related protein-1 (LRP-1, an LDL receptor family member); tPA-mediated in vitro and ex vivo clot lysis; and tPA-mediated plasminogen activation in the absence and presence of a stimulating soluble fibrin fragment. Two aptamers, K18 and K32, had minimal effects on clot lysis, but were able to efficiently inhibit tPA-LRP-1 association and LDL receptor family-mediated endocytosis in human vascular endothelial cells and astrocytes. These observations suggest that coadministration alongside tPA may be a viable strategy to improve the safety of thrombolytic treatment of cerebral ischaemic stroke by restricting tPA activity to the vascular lumen.

Geraniol attenuates 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammation in mouse skin: possible role of p38 MAP Kinase and NF-κB.

Science.gov (United States)

Khan, Abdul Quaiyoom; Khan, Rehan; Qamar, Wajhul; Lateef, Abdul; Rehman, Muneeb U; Tahir, Mir; Ali, Farrah; Hamiza, Oday O; Hasan, Syed Kazim; Sultana, Sarwat

2013-06-01

Abnormal production of reactive oxygen species (ROS) and proinflammatory cytokines often act as trigger for development of most of the chronic human diseases including cancer via up-regulation of transcription factors and activation of MAP kinases. We investigated the protective effects of geraniol (GOH) against 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced oxidative and inflammatory responses, expression of p38MAPK, NF-κB and COX-2 in mouse skin. Animals were divided into four groups I-IV (n=6). Group II and III received topical application of TPA at the dose of 10 nmol/0.2 ml of acetone/animal/day, for two days. Group III was pre-treated with GOH (250 μg) topically 30 min prior to each TPA administration. While group I and IV were given acetone (0.2 ml) and GOH respectively. Our results show that GOH significantly inhibited TPA induced lipid peroxidation (LPO), inflammatory responses, proinflammatory cytokine release, up regulates reduced glutathione (GSH) content and the activity of different antioxidant enzymes. Interestingly, GOH also inhibited TPA induced altered activity of p38MAPK. Further, TPA induced altered expression of NF-κB (p65) and COX-2 was also attenuated by GOH. Thus, our results suggest that GOH attenuates early tumor promotional changes, and it may serve as one of the various ways to prevent carcinogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Communicative Learning Outcomes and World Language edTPA: Characteristics of High-Scoring Portfolios

Science.gov (United States)

Swanson, Pete; Hildebrandt, Susan A.

2017-01-01

Teacher accountability continues to be at the forefront of educational policy in the United States, with the current focus on the Outcomes of K-12 teaching and teacher education (Cochran-Smith 2000). edTPA, a high-stakes assessment used in many states to make licensure or certification decisions, purports to measure those content-specific…

In vitro assessment of Tc-99m labeled bovine thrombin and streptokinase-activated human plasmin: concise communication

International Nuclear Information System (INIS)

Wong, D.W.; Tanaka, T.; Mishkin, F.; Lee, T.

1979-01-01

Bovine thrombin and streptokinase-activated human plasmin have been labeled with Tc-99m using stannous reduction of pertechnetate under physiological conditions (pH 7.4). The binding efficiency of radiotechnetium to these enzymes is greater than 94%, with less than 5% of reduced but unbound Tc-99m (Sn) complex as assayed by ascending paper radiochromatography using ITLC silica gel plate. Free or unbound pertechnetate is less than 1%. In vitro enzymatic analyses of the Tc-99m-labeled enzymes demonstrate no evidence of protein denaturation or significant loss of enzymatic activity after labeling. Both labeled enzymes are biochemically active in vitro with their respective substrates

Tensile properties of cooked meat sausages and their correlation with texture profile analysis (TPA) parameters and physico-chemical characteristics.

Science.gov (United States)

Herrero, A M; de la Hoz, L; Ordóñez, J A; Herranz, B; Romero de Ávila, M D; Cambero, M I

2008-11-01

The possibilities of using breaking strength (BS) and energy to fracture (EF) for monitoring textural properties of some cooked meat sausages (chopped, mortadella and galantines) were studied. Texture profile analysis (TPA), folding test and physico-chemical measurements were also performed. Principal component analysis enabled these meat products to be grouped into three textural profiles which showed significant (p<0.05) differences mainly for BS, hardness, adhesiveness and cohesiveness. Multivariate analysis indicated that BS, EF and TPA parameters were correlated (p<0.05) for every individual meat product (chopped, mortadella and galantines) and all products together. On the basis of these results, TPA parameters could be used for constructing regression models to predict BS. The resulting regression model for all cooked meat products was BS=-0.160+6.600∗cohesiveness-1.255∗adhesiveness+0.048∗hardness-506.31∗springiness (R(2)=0.745, p<0.00005). Simple linear regression analysis showed significant coefficients of determination between BS (R(2)=0.586, p<0.0001) versus folding test grade (FG) and EF versus FG (R(2)=0.564, p<0.0001).

Kualitas Hidup Komunitas Pemulung di Tempat Pembuangan Akhir (TPA Air Dingin Kota Padang di Tinjau dari Segi Pendidikan

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Wati

2015-10-01

Full Text Available This paper analyzes about life quality of scavenger community in the final disposal (TPA Air Dingin Balai Gadang District Koto Tangah Village Padang. Scavengers are people who work collecting scrap things that are not longer useful by households, markets, offices, which have economic value. The research aims to reveal about the life quality of scavenger community in the final disposal Air Dingin seen from the aspect of education. Research methodology used is a qualitative approach. The data collection methods used are observation, interviews, documentation. The Informant sellected by using purposive sampling technique. The informants in this study are a scavenger community in TPA Air Dingin. The technique ensures of the data validation are refered to the use of Lincoln and Guba standard, namely credibility, transferability, dependability, conformability. Data analysis techniques are used data reduction step, data presentation, and conclusion. The results of this research revealed that scavengers have a high motivation to be able to change the fate out of poverty that has been felt, whatever they will done to educate their children and raise a family. They have high spirit, not affected by the weather, they still go to the trash in the morning in order to get more results, which means getting more money. It has been apparent the change of scavengers lives in the landfill of Air Dingin towards a better life, even it takes long time.

Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

Science.gov (United States)

Noh, Eun-Mi; Park, Yeon-Ju; Kim, Jeong-Mi; Kim, Mi-Seong; Kim, Ha-Rim; Song, Hyun-Kyung; Hong, On-Yu; So, Hong-Seob; Yang, Sei-Hoon; Kim, Jong-Suk; Park, Samg Hyun; Youn, Hyun-Jo; You, Yong-Ouk; Choi, Ki-Bang; Kwon, Kang-Beom; Lee, Young-Rae

2015-10-05

Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis. Copyright © 2015 Elsevier B.V. All rights reserved.

A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κ3N)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli.

Science.gov (United States)

Rana, Namrata; Jesse, Helen E; Tinajero-Trejo, Mariana; Butler, Jonathan A; Tarlit, John D; von Und Zur Muhlen, Milena L; Nagel, Christoph; Schatzschneider, Ulrich; Poole, Robert K

2017-10-01

Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ 3 N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ 3 N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ 3 N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ 3 N)]Br.

Gender affects skin wound healing in plasminogen deficient mice.

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Birgitte Rønø

Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

Optimized production technology (OPT), theory of constraints (TOC) og den dertil hørende økonomistyringstankegang 'Throughput Accounting (TPA)'

DEFF Research Database (Denmark)

Nielsen, Steen; Hansen, Tom Albæk

2005-01-01

Kombinationen af økonomistyring med forskellige andre funktionsområder, f.eks., indkøb, produktion, afsætning, adfærd etc., er et vigtigt område, og udgør efterhånden en del af det pensum, som repræsenteres i diverse lærebøger indenfor cost management accounting. OPT, TOC, TPA, samt også modeller...... som Just-In-Time (JIT) og Life-Cycle-Costing (LCC) vil fremover kunne give inspiration til nye måder at anskue økonomistyringen på. TOC, JIT og LCC kombineres ofte, både i relation til de mere operative beslutninger, men også i relation til virksomhedens strategiledelse. Ideen er, at også de...... separat eller i kombination. På denne måde bør de kunne støtte virksomhedens strategi og dermed den samlede lønsomhed. Hvor OPT sætter fokus på at optimere produktionen, sætter TOC og TPA fokus på udnyttelse af produktionsapparatet og på likviditeten. TPA minder på mange måder om bidragsmodellen og den...

Serum creatinine may indicate risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator (IV tPA).

Science.gov (United States)

Marsh, Elisabeth B; Gottesman, Rebecca F; Hillis, Argye E; Urrutia, Victor C; Llinas, Rafael H

2013-11-01

Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient's neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a "symptomatic" hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR creatinine >1.0 mg/dL) was not associated with combined symptomatic and asymptomatic intracranial bleeding (p = 0.359); however, there was an adjusted 5.5-fold increased odds of sICH when creatinine was >1.0 mg/dL (95% confidence interval, 1.08-28.39), and the frequency of s

Basic Evaluation of the Newly Developed "Lias Auto P-FDP" Assay and the Influence of Plasmin-α2 Plasmin Inhibitor Complex Values on Discrepancy in the Comparison with "Lias Auto D-Dimer Neo" Assay.

Science.gov (United States)

Kumano, Osamu; Ieko, Masahiro; Komiyama, Yutaka; Naito, Sumiyoshi; Yoshida, Mika; Takahashi, Nobuhiko; Ohmura, Kazumasa; Hayasaki, Junki; Hayakawa, Mineji

2018-04-01

Laboratory determination of fibrin/fibrinogen degradation products (FDP) levels, along with that of the D-dimer, is important for assessing the fibrinolytic situation. Recently, we developed a new FDP reagent "Lias Auto P-FDP", which can detect various FDP fragments. The purpose of this study was to evaluate the basic performance of the newly developed Lias Auto P-FDP and compare it with Lias Auto D-Dimer Neo assay. The within-run precision of Lias Auto P-FDP and Lias Auto D-Dimer was determined 20 times in low and high value controls. The between-day precision was evaluated five times a day for five days. The linearity study was performed by diluting high value samples for 2 - 10-fold and 2 - 8-fold. The comparative study was performed using 172 patient samples with elevated FDP values. For the discrepancy analysis, the samples were divided into three groups by the discrepancy percentage between the FDP and D-dimer values. The groups were defined as follows: lower discrepancy group, less than -20%; no discrepancy group, -20% to 20%; upper discrepancy group, more than 20%. The coefficient of variation % (CV%) in within-run and between-day precision were within 3.8% for both FDP and the D-dimer. The correlation coefficients were more than 0.999 and the linearity was high. In the comparative study, the values of FDP were higher than that of the D-dimer in all samples. The median FDP and D-dimer values of lower discrepancy, no discrepancy, and upper discrepancy groups were 11.8, 20.3, and 51.4, and 8.0, 11.3, and 13.1, respectively. FDP showed an increasing tendency but D-Dimer showed constant values. Thus, the possible cause of discrepancy between FDP and D-dimer values were the elevated FDP values. In addition, the values of plasmin-α2 plasmin inhibitor complex (PIC) in the upper discrepancy group were higher than that of the lower and no discrepancy groups, indicating progression of fibrinolysis. In this study, we evaluated the newly developed Lias Auto P

FITOREMEDIASI KADMIUM (CD PADA LEACHATE MENGGUNAKAN KANGKUNG AIR (Ipomoea aquatica Forsk. (STUDI KASUS TPA JATIBARANG

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K N Zamhar

2016-03-01

Full Text Available Leachate TPA Jatibarang yang tercemar kadmium (Cd kemungkinan dapat dibersihkan secara fitoremediasi menggunakan kangkung air (Ipomoea aquatica Forsk.. Penelitian ini bertujuan untuk mengetahui kemampuan kangkung air sebagai fitoremediator dalam menyerap Cd dalam leachate TPA Jatibarang. Sebelum penelitian, dilakukan uji pendahuluan kandungan Cd dalam leachate maupun dalam kangkung air. Kangkung diaklimatisasi dalam air bersih selama 3 hari, selanjutnya ditimbang seberat 300 gram kemudian diletakkan ke dalam ember berisi 10 L leachate. Sampel leachate dan organ tanaman diambil setiap 2 hari sekali (2 hari, 4 hari, 6 hari, dan 8 hari. Faktor intensitas cahaya diambil setiap hari pada pukul 08.00-09.00 WIB menggunakan lux meter, sedangkan nilai pH dan suhu leachate diukur menggunakan kertas indikator pH dan termometer sebelum dan sesudah perlakuan. Perameter yang diamati adalah akumulasi Cd dalam akar, batang, dan daun kangkung air pada masing-masing lama waktu pananaman. Akumulasi Cd diukur dengan AAS (Atomic Absorption Spectrophotometry. Data penyerapan Cd dianalisis secara deskriptif. Hasil penelitian menunjukkan bahwa lama waktu kangkung air ditanam dalam leachate berpengaruh terhadap akumulasi Cd pada tanaman. Penyerapan Cd oleh kangkung air mencapai jenuh pada hari ke-8 dengan total penyerapan 0,052 ppm. Akumulasi Cd paling besar pada akar kangkung yaitu 0,023 ppm.Cadmium (Cd that contained in TPA Jatibarang’s leachate can be cleaned by phytoremediation using water spinach (Ipomoea aquatica Forsk.. This research aimed to determine the ability of the water spinach as a fitoremediator in adsorb cadmium (Cd that contained in TPA Jatibarang’s leachate. The research was conducted by using a randomized completely design (RCD factorial, with longer treatment planted time in leachate water spinach was 0 day, 2 days, 4 days, 6 days, and 8 days respectively. The observed parameters of Cd accumulation in roots, stems, and leaves of water spinach in

Polarization dependence of two-photon absorption coefficient and nonlinear susceptibility tensor in InP

International Nuclear Information System (INIS)

Matsusue, Toshio; Bando, Hiroyuki; Fujita, Shoichi; Takayama, Yusuke

2011-01-01

Two-photon absorption (TPA) effect in (001) InP is investigated using fs laser. Its dependences on wavelength and polarization are clarified by single and double beam methods with linearly polarized lights. Characteristic features are revealed and discussed with scaling law, crystal bonding and mutual relation of polarizations for double beams. The results are successfully analyzed on the basis of the third-order susceptibility tensor for comprehensive understanding of TPA effect at any polarization geometry. (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling.

Science.gov (United States)

Sun, X; Lu, B; Hu, B; Xiao, W; Li, W; Huang, Z

2014-03-28

12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was the major activator of C7ORF41 that in turn repressed NF-κB activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation.

Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling

International Nuclear Information System (INIS)

Sun, X; Lu, B; Hu, B; Xiao, W; Li, W; Huang, Z

2014-01-01

12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was the major activator of C7ORF41 that in turn repressed NF-κB activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation

In vitro assessment of Tc-99m labeled bovine thrombin and streptokinase-activated human plasmin: concise communication. [Iodine 125

Energy Technology Data Exchange (ETDEWEB)

Wong, D.W.; Tanaka, T.; Mishkin, F.; Lee, T.

1979-09-01

Bovine thrombin and streptokinase-activated human plasmin have been labeled with Tc-99m using stannous reduction of pertechnetate under physiological conditions (pH 7.4). The binding efficiency of radiotechnetium to these enzymes is greater than 94%, with less than 5% of reduced but unbound Tc-99m (Sn) complex as assayed by ascending paper radiochromatography using ITLC silica gel plate. Free or unbound pertechnetate is less than 1%. In vitro enzymatic analyses of the Tc-99m-labeled enzymes demonstrate no evidence of protein denaturation or significant loss of enzymatic activity after labeling. Both labeled enzymes are biochemically active in vitro with their respective substrates.

Immunohistochemical study of tumor markers (CEA, TPA, CA19-9, POA and Ferritin) and pancreatic exocrine enzymes(Amylase and Elastase 1) in pancreatic tumors

OpenAIRE

脇谷, 勇夫

1987-01-01

The distribution of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), pancreatic oncofetal antigen (POA), Ferritin, Amylase and Elastase 1 was studied immunohistochemically using an immunoperoxidase method in 26 conventional histopathologic sections of pancreatic tumor. CEA and CA19-9 were regarded as markers secreted into the glandular lumina from cancer cells, but TPA and POA were not. The expression of these markers was different from one...

An Examination of the EeTPA Portfolio Assessment and Other Measures of Teacher Preparation and Readiness

Science.gov (United States)

Russell, Victoria; Davidson Devall, Kelly F.

2016-01-01

The authors examined the outcomes on several measures of world language teacher preparedness, including university- and state-mandated summative evaluations and the edTPA portfolio assessment, for seven world language teacher candidates during their final semester of clinical practice. The candidates were enrolled in an initial certification…

Effects of garlic on cellular doubling time and DNA strand breaks caused by UV light and BPL, enhanced with catechol and TPA

International Nuclear Information System (INIS)

Baturay, N.Z.; Gayle, F.; Liu, S.; Kreidinger, C.

1995-01-01

3T3 cell cultures were exposed to UV light and Beta-Propiolactone. Neoplastic cell transformation (TF) was demonstrated after concurrent addition of catechol, or repeated addition of TPA. Addition of garlic to all fluences/concentrations of the carcinogen/cocarcinogen/promoter groups reduced the number of transformed foci/dish by at least 40%. Since the cell cycle is prolonged following exposure to carcinogens, it is likely the cell requires a longer time to repair this damage. The doubling time (DT) was extended from 12 to 36 hrs. when cells were exposed to BPL and from 12 o 28 hrs. when cells were exposed to 3.0J/M2/sec. If an anticarcinogenic compound is also added, it is reasonable to assume that the cell cycle may be further elongated. The cell cycle, denoted by DT was lengthened from 12 to 47 hrs and from 12 to 86 hrs for BPL and UVC, respectively. The extensions occurred in a dope dependent manner. The concentrations of the cocarcinogen and promoter remained constant throughout the experiment. When strand breaks were determined at the same dose sequences, by alkaline elution, more repair was seen with garlic where the lowest and middle doses of BPL were used and almost no decrease in % DNA eluted was seen with UVC exposed cells. With catechol, there was a two-fold decrease in % DNA eluted at the lowest and middle fluences. When TPA was added, all three fluences of UVC showed more than a threefold decrease in % DNA eluted. BPS with both TPA and catechol, again showed a reduction in strand breaks only low and middle doses. Both a direct-acting alkylating agent, BPL, and a physical carcinogen, UVC, were homogeneously affected, in terms of doubling time, but not when strand break repair was examined. A separate mechanism may be responsible for repair, and the mechanism associated with combinations of physical carcinogen enhancing agents combined with some non-carcinogens may be more profoundly affected by some natural products

Relação entre atividade de plasmina e frações de caseína durante o armazenamento do leite longa vida Relationship between plasmin activity and casein fractions during storage of UHT milk

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Carlos Humberto Corassin

2013-03-01

Full Text Available Este estudo teve como objetivo correlacionar a atividade da plasmina e as concentrações de frações de caseína no leite longa vida (UAT produzido em usina de beneficiamento do Estado de São Paulo. O leite cru foi submetido à pasteurização (72-76 ºC, 15-20 segundos, seguida da esterilização por processo de injeção direta de vapor (132-136 ºC, 34 segundos, sendo homogeneizado e envasado assepticamente em embalagens cartonadas. Quatro lotes de UAT foram analisados para atividade de plasmina e frações de caseína após 10, 30, 60, 90 e 120 dias de armazenamento. A atividade de plasmina no leite longa vida aumentou durante o armazenamento, correlacionando-se negativamente com a concentração de αs1-caseína. A atividade da plasmina apresenta resistência à esterilização do leite pelo processo UAT e aumenta a proteólise do leite longa vida como consequência da degradação da αs1-caseína.The objective of this study was to correlate the plasmin activity and the concentrations of casein fractions in ultra-high-temperature (UHT milk manufactured in a dairy plant in the State of Sao Paulo, Brazil. Raw milk was pasteurized (72-76 ºC, 15-20 seconds, followed by direct steam injection into the milk (132-136 ºC, 34 seconds, then homogenized and aseptically packaged into cartons. Four replicates of the UHT milk were analyzed for the plasmin activity and casein fractions after 10, 30, 60, 90 and 120 days of storage. Plasmin activity significantly increased in the UHT milk during storage and was negatively correlated with the concentration of αs1-casein. Plasmin is resistant to milk sterilization by the UHT process, and increases proteolysis of the UHT milk as a consequence of αs1-casein degradation.

Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice

DEFF Research Database (Denmark)

Lund, Leif R; Green, Kirsty A; Stoop, Allart A

2006-01-01

Simultaneous ablation of the two known activators of plasminogen (Plg), urokinase-type (uPA) and the tissue-type (tPA), results in a substantial delay in skin wound healing. However, wound closure and epidermal re-epithelialization are significantly less impaired in uPA;tPA double-deficient mice ...

Fibrinolysis and proliferative endarteritis: two related processes in chronic infections? The model of the blood-borne pathogen Dirofilaria immitis.

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Javier González-Miguel

Full Text Available The interaction between blood-borne pathogens and fibrinolysis is one of the most important mechanisms that mediate invasion and the establishment of infectious agents in their hosts. However, overproduction of plasmin (final product of the route has been related in other contexts to proliferation and migration of the arterial wall cells and degradation of the extracellular matrix. We have recently identified fibrinolysis-activating antigens from Dirofilaria immitis, a blood-borne parasite whose key pathological event (proliferative endarteritis is produced by similar mechanisms to those indicated above. The objective of this work is to study how two of this antigens [actin (ACT and fructose-bisphosphate aldolase (FBAL] highly conserved in pathogens, activate fibrinolysis and to establish a relationship between this activation and the development of proliferative endarteritis during cardiopulmonary dirofilariasis. We demonstrate that both proteins bind plasminogen, enhance plasmin generation, stimulate the expression of the fibrinolytic activators tPA and uPA in endothelial cell cultures and are located on the surface of the worm in contact with the host's blood. ELISA, western blot and immunofluorescence techniques were employed for this purpose. Additionally, the implication of lysine residues in this interaction was analyzed by bioinformatics. The involvement of plasmin generated by the ACT/FBAL and plasminogen binding in cell proliferation and migration, and degradation of the extracellular matrix were shown in an "in vitro" model of endothelial and smooth muscle cells in culture. The obtained results indicate that ACT and FBAL from D. immitis activate fibrinolysis, which could be used by the parasite like a survival mechanism to avoid the clot formation. However, long-term overproduction of plasmin can trigger pathological events similar to those described in the emergence of proliferative endarteritis. Due to the high degree of

Fibrin accumulation secondary to loss of plasmin-mediated fibrinolysis drives inflammatory osteoporosis in mice.

Science.gov (United States)

Cole, Heather A; Ohba, Tetsuro; Nyman, Jeffry S; Hirotaka, Haro; Cates, Justin M M; Flick, Matthew J; Degen, Jay L; Schoenecker, Jonathan G

2014-08-01

Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. Copyright © 2014 by the American College of Rheumatology.

What Does It Mean to Be Student Centered? An Institutional Case Study of edTPA Implementation

Science.gov (United States)

Fayne, Harriet; Qian, Gaoyin

2016-01-01

This longitudinal case study investigated how one School of Education (SOE), situated in an urban, commuter, public university, responded to the New York State mandate to require the edTPA for initial teacher certification. In order to engage faculty in the work of program redesign, SOE administrators employed a covert leadership approach. Based…

Endogenous fibrinolysis facilitates clot retraction in vivo.

Science.gov (United States)

Samson, Andre L; Alwis, Imala; Maclean, Jessica A A; Priyananda, Pramith; Hawkett, Brian; Schoenwaelder, Simone M; Jackson, Shaun P

2017-12-07

Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated platelet contractility prevented shrinkage of the fibrin network. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. These effects correlated with changes in the elastic modulus of fibrin clots. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size. © 2017 by The American Society of Hematology.

Exploratory Content Analysis of Candidates' Perspectives on Multicultural Education as Evidenced in Their edTPA Portfolios

Science.gov (United States)

Cannon, Sarah

2016-01-01

This exploratory qualitative content analysis examined the edTPA portfolios of 36 randomly selected teacher candidates to address a national trend towards standardization and accountability in teacher education in relationship to the critical need for multicultural educators. Using multicultural education as a theoretical framework, this study…

Utilization Of Seeds Durian (Durio Zibethinus Murr) Powder AS Biopolymer Additional Materials Of Coagulant Alum To Improve The Total Solids Removal Suspended (Tss) And Cod Using Leachate Coagulation-flocculation (Studi Kasus: Tpa Jatibarang, Kota Semaran

OpenAIRE

Alfa Christianty, Dina; Zaman, Badrus; Purwono, Purwono

2017-01-01

TPA Jatibarang menjadi salah satu sumber limbah cair di Semarang di mana lokasinya dekat dengan pemukiman penduduk. Limbah cair yang dihasilkan dari Tempat Pemrosesan Akhir (TPA) sampah berupa air yang dihasilkan dari timbunan sampah yang disebut air lindi (leachate). Lindi TPA Jatibarang umumnya memiliki kandungan senyawa organik yang tinggi dan keberadaannya yang melebihi baku mutu dapat mencemari lingkungan sekitar apabila tidak dilakukan pengolahan terlebih dahulu. Pengolahan lindi mengg...

Predictive performance of TPA testing for recurrent disease during follow-up after curative intent surgery for colorectal carcinoma

NARCIS (Netherlands)

van der Sluis, Frederik J.; Zhan, Zhuozhao; Verberne, Charlotte J.; Muller Kobold, Anneke C.; Wiggers, Theo; de Bock, Geertruida H.

Background: The aim of the present study was to investigate the predictive performance of serial tissue polypeptide antigen (TPA) testing after curative intent resection for detection of recurrence of colorectal malignancy. Methods: Serum samples were obtained in 572 patients from three different

Abalone Muscle Texture Evaluation and Prediction Based on TPA Experiment

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Jiaxu Dong

2017-01-01

Full Text Available The effects of different heat treatments on abalones’ texture properties and sensory characteristics were studied. Thermal processing of abalone muscle was analyzed to determine the optimal heat treatment condition based on fuzzy evaluation. The results showed that heat treatment at 85°C for 1 hour had certain desirable effects on the properties of the abalone meat. Specifically, a back propagation (BP neural network was introduced to predict the equations of statistically significant sensory hardness, springiness, and smell using the texture data gained through TPA (texture profile analysis experiments as input and sensory evaluation data as the desired output. The final outcome was that the predictability was proved to be satisfactory, with an average error of 6.93%.

Gender affects skin wound healing in plasminogen deficient mice

DEFF Research Database (Denmark)

Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge

2013-01-01

closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds...... functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency...... or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation...

The chain of care enabling tPA treatment in acute ischemic stroke : a comprehensive review of organisational models

NARCIS (Netherlands)

Lahr, Maarten M. H.; Luijckx, Gert-Jan; Vroomen, Patrick; van der Zee, D.J.; Buskens, Erik

Protracted and partial implementation of treatment with intravenous tissue plasminogen activator (tPA) within 4.5 h after acute stroke onset results in potentially eligible patients not receiving optimal treatment. The goal of this study was to review the performance of various organisational models

Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells.

OpenAIRE

Okuda, A; Imagawa, M; Sakai, M; Muramatsu, M

1990-01-01

We have recently identified an enhancer, termed GPEI, in the 5'-flanking region of the rat glutathione transferase P gene, that is composed of two imperfect TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive elements (TREs). Unlike other TRE-containing enhancers, GPEI exhibits a strong transcriptional enhancing activity in F9 embryonic stem cells. Mutational analyses have revealed that the high activity of GPEI is mediated by two imperfect TREs. Each TRE-like sequence has no activity by ...

Potensi Material Sampah Combustible pada Zona Pasif TPA Jatibarang Semarang sebagai Bahan Baku RDF (Refuse Derived Fuel

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Irma Natasya Hutabarat

2018-03-01

Full Text Available Abstrak: Peningkatan jumlah timbulan sampah menyebabkan meningkatnya kebutuhan lahan pada TPA Jatibarang. Untuk menghindari terjadinya kekurangan lahan perlu dilakukan penanganan pada sampah yakni dengan mengubah sampah menjadi sumber energi seperti bahan baku RDF (Refused Derived Fuel. RDF merupakan salah satu teknik penanganan sampah dengan mengubah sampah menjadi sesuatu yang bermanfaat yaitu bahan bakar. Sampah tersebut dapat dimanfaatkan menjadi bahan baku RDF dengan cara menganalisis nilai kalor yang dihasilkan. Untuk menganalisis nilai kalor pada sampah combustible zona pasif TPA Jatibarang dapat dilakukan dengan cara pengujian sampel sebanyak 100 gram dengan alat bom kalorimeter. Sampel tersebut diambil pada kedalaman 0-3 m dengan metode random sampling. Kemudian akan didapat nilai kalor tinggi yang dihasilkan sampel tersebut. Nilai Kalor Tinggi yang dihasilkan sampel tersebut sebesar 5,25 kkal/ton pada kedalaman 0-1 m, 5,76 kkal/ton pada kedalaman 1-2 m dan 6,31 kkal/ton pada kedalaman 2-3 m. Nilai kalor tinggi yang dihasilkan sampah combustible tersebut menunjukkan bahwa semakin rendah kedalaman sampah maka akan semakin tinggi nilai kalor yang dihasilkan dan sampah tersebut berpotensi sebagai bahan baku RDF.

The Plasmin-Sensitive Protein Pls in Methicillin-Resistant Staphylococcus aureus (MRSA Is a Glycoprotein.

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Isabelle Bleiziffer

2017-01-01

Full Text Available Most bacterial glycoproteins identified to date are virulence factors of pathogenic bacteria, i.e. adhesins and invasins. However, the impact of protein glycosylation on the major human pathogen Staphylococcus aureus remains incompletely understood. To study protein glycosylation in staphylococci, we analyzed lysostaphin lysates of methicillin-resistant Staphylococcus aureus (MRSA strains by SDS-PAGE and subsequent periodic acid-Schiff's staining. We detected four (>300, ∼250, ∼165, and ∼120 kDa and two (>300 and ∼175 kDa glycosylated surface proteins with strain COL and strain 1061, respectively. The ∼250, ∼165, and ∼175 kDa proteins were identified as plasmin-sensitive protein (Pls by mass spectrometry. Previously, Pls has been demonstrated to be a virulence factor in a mouse septic arthritis model. The pls gene is encoded by the staphylococcal cassette chromosome (SCCmec type I in MRSA that also encodes the methicillin resistance-conferring mecA and further genes. In a search for glycosyltransferases, we identified two open reading frames encoded downstream of pls on the SCCmec element, which we termed gtfC and gtfD. Expression and deletion analysis revealed that both gtfC and gtfD mediate glycosylation of Pls. Additionally, the recently reported glycosyltransferases SdgA and SdgB are involved in Pls glycosylation. Glycosylation occurs at serine residues in the Pls SD-repeat region and modifying carbohydrates are N-acetylhexosaminyl residues. Functional characterization revealed that Pls can confer increased biofilm formation, which seems to involve two distinct mechanisms. The first mechanism depends on glycosylation of the SD-repeat region by GtfC/GtfD and probably also involves eDNA, while the second seems to be independent of glycosylation as well as eDNA and may involve the centrally located G5 domains. Other previously known Pls properties are not related to the sugar modifications. In conclusion, Pls is a glycoprotein and

Functional properties of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli

International Nuclear Information System (INIS)

Wilhelm, O.G.; Jaskunas, S.R.; Vlahos, C.J.; Bang, N.U.

1990-01-01

The kringle-2 domain (residues 176-262) of tissue-type plasminogen activator (t-PA) was cloned and expressed in Escherichia coli. The recombinant peptide, which concentrated in cytoplasmic inclusion bodies, was isolated, solubilized, chemically refolded, and purified by affinity chromatography on lysine-Sepharose to apparent homogeneity. [35S]Cysteine-methionine-labeled polypeptide was used to study the interactions of kringle-2 with lysine, fibrin, and plasminogen activator inhibitor-1. The kringle-2 domain bound to lysine-Sepharose and to preformed fibrin with a Kd = 104 +/- 6.2 microM (0.86 +/- 0.012 binding site) and a Kd = 4.2 +/- 1.05 microM (0.80 +/- 0.081 binding site), respectively. Competition experiments and direct binding studies showed that the kringle-2 domain is required for the formation of the ternary t-PA-plasminogen-intact fibrin complex and that the association between the t-PA kringle-2 domain and fibrin does not require plasmin degradation of fibrin and exposure of new COOH-terminal lysine residues. We also observed that kringle-2 forms a complex with highly purified guanidine-activated plasminogen activator inhibitor-1, dissociable by 0.2 M epsilon-aminocaproic acid. The kringle-2 polypeptide significantly inhibited tissue plasminogen activator/plasminogen activator inhibitor-1 interaction. The kringle-2 domain bound to plasminogen activator inhibitor-1 in a specific and saturable manner with a Kd = 0.51 +/- 0.055 microM (0.35 +/- 0.026 binding site). Therefore, the t-PA kringle-2 domain is important for the interaction of t-PA not only with fibrin, but also with plasminogen activator inhibitor-1 and thus represents a key structure in the regulation of fibrinolysis

Uso do TPA e gás intravítreo no tratamento da hemorragia sub-retiniana bilateral: Relato de Caso

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Serracarbassa Pedro Duraes

2002-01-01

Full Text Available Objetivo: O autor descreve um caso de hemorragia sub-retiniana e subepitélio pigmentado da retina (EPR bilateral, secundária a degeneração macular relacionada à idade, tratada com injeção intravítrea de ativador do plasminogênio tecidual (tPA e gás perfluoropropano (C3F8. Relato do caso: Dois olhos de um paciente portador de hemorragia sub-retiniana macular e sub-EPR foram tratados com injeções intravítreas de 25 mig de tPA e 0,3 mL de C3F8. Avaliaram-se a acuidade visual e o aspecto da retinografia e angiofluoresceinografia pré e pós-operatória. Resultados: Uma semana após as injeções, os dois olhos apresentaram resolução completa da hemorragia subfoveal, porém resquícios de hemorragia sub-retiniana perimacular foram observados, mais acentuados no olho esquerdo. A hemorragia sub-EPR localizada no olho esquerdo, não apresentou sinais de melhora. A acuidade visual apresentou melhora em ambos os olhos, principalmente no olho direito. Conclusão: A injeção intravítrea de tPA associada ao C3F8 apresenta-se como uma alternativa viável no tratamento da hemorragia sub-retiniana secundária a DMRI, porém hemorragias situadas abaixo do EPR ainda permanecem um desafio terapêutico. Estudos futuros são necessários.

Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells.

Science.gov (United States)

Kim, Jeong-Mi; Noh, Eun-Mi; Song, Hyun-Kyung; Lee, Minok; Lee, Soo Ho; Park, Sueng Hyuk; Ahn, Chan-Keun; Lee, Guem-San; Byun, Eui-Baek; Jang, Beom-Su; Kwon, Kang-Beom; Lee, Young-Rae

2017-09-01

Cancer cell invasion is crucial for metastasis. A major factor in the capacity of cancer cell invasion is the activation of matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix. Salvia miltiorrhiza has been used as a promotion for blood circulation to remove blood stasis. Numerous previous studies have demonstrated that S. miltiorrhiza extracts (SME) decrease lipid levels and inhibit inflammation. However, the mechanism behind the effect of SME on breast cancer invasion has not been identified. The inhibitory effects of SME on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression were assessed using western blotting, reverse transcription-quantitative polymerase chain reaction and zymography assays. MMP-9 upstream signal proteins, including mitogen-activated protein kinases and activator protein 1 (AP-1) were also investigated. Cell invasion was assessed using a matrigel invasion assay. The present study demonstrated the inhibitory effects of the SME ethanol solution on MMP-9 expression and cell invasion in TPA-treated MCF-7 breast cancer cells. SME suppressed TPA-induced MMP-9 expression and MCF-7 cell invasion by blocking the transcriptional activation of AP-1. SME may possess therapeutic potential for inhibiting breast cancer cell invasiveness.

Time-dependent density functional theory study of the luminescence properties of gold phosphine thiolate complexes.

Science.gov (United States)

Guidez, Emilie B; Aikens, Christine M

2015-04-09

The origin of the emission of the gold phosphine thiolate complex (TPA)AuSCH(CH3)2 (TPA = 1,3,5-triaza-7-phosphaadamantanetriylphosphine) is investigated using time-dependent density functional theory (TDDFT). This system absorbs light at 3.6 eV, which corresponds mostly to a ligand-to-metal transition with some interligand character. The P-Au-S angle decreases upon relaxation in the S1 and T1 states. Our calculations show that these two states are strongly spin-orbit coupled at the ground state geometry. Ligand effects on the optical properties of this complex are also discussed by looking at the simple AuP(CH3)3SCH3 complex. The excitation energies differ by several tenths of an electronvolt. Excited state optimizations show that the excited singlet and triplet of the (TPA)AuSCH(CH3)2 complex are bent. On the other hand, the Au-S bond breaks in the excited state for the simple complex, and TDDFT is no longer an adequate method. The excited state energy landscape of gold phosphine thiolate systems is very complex, with several state crossings. This study also shows that the formation of the [(TPA)AuSCH(CH3)2]2 dimer is favorable in the ground state. The inclusion of dispersion interactions in the calculations affects the optimized geometries of both ground and excited states. Upon excitation, the formation of a Au-Au bond occurs, which results in an increase in energy of the low energy excited states in comparison to the monomer. The experimentally observed emission of the (TPA)AuSCH(CH3)2 complex at 1.86 eV cannot be unambiguously assigned and may originate from several excited states.

Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator- dependent gelatinase activation in mice neonate brain microvessels.

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Priscilla L Omouendze

Full Text Available Hypoxia-ischemia (HI and excitotoxicity are validated causes of neonatal brain injuries and tissue plasminogen activator (t-PA participates in the processes through proteolytic and receptor-mediated pathways. Brain microvascular endothelial cells from neonates in culture, contain and release more t-PA and gelatinases upon glutamate challenge than adult cells. We have studied t-PA to gelatinase (MMP-2 and MMP-9 activity links in HI and excitotoxicity lesion models in 5 day-old pups in wild type and in t-PA or its inhibitor (PAI-1 genes inactivated mice. Gelatinolytic activities were detected in SDS-PAGE zymograms and by in situ fluorescent DQ-gelatin microscopic zymographies. HI was achieved by unilateral carotid ligature followed by a 40 min hypoxia (8%O₂. Excitotoxic lesions were produced by intra parenchymal cortical (i.c. injections of 10 µg ibotenate (Ibo. Gel zymograms in WT cortex revealed progressive extinction of MMP-2 and MMP-9 activities near day 15 or day 8 respectively. MMP-2 expression was the same in all strains while MMP-9 activity was barely detectable in t-PA⁻/⁻ and enhanced in PAI-1⁻/⁻ mice. HI or Ibo produced activation of MMP-2 activities 6 hours post-insult, in cortices of WT mice but not in t-PA⁻/⁻ mice. In PAI-1⁻/⁻ mice, HI or vehicle i.c. injection increased MMP-2 and MMP-9 activities. In situ zymograms using DQ-gelatin revealed vessel associated gelatinolytic activity in lesioned areas in PAI-1⁻/⁻ and in WT mice. In WT brain slices incubated ex vivo, glutamate (200 µM induced DQ-gelatin activation in vessels. The effect was not detected in t-PA⁻/⁻ mice, but was restored by concomitant exposure to recombinant t-PA (20 µg/mL. In summary, neonatal brain lesion paradigms and ex vivo excitotoxic glutamate evoked t-PA-dependent gelatinases activation in vessels. Both MMP-2 and MMP-9 activities appeared t-PA-dependent. The data suggest that vascular directed protease inhibition may have

Assessment of biological variation and analytical imprecision of CA 125, CEA, and TPA in relation to monitoring of ovarian cancer

DEFF Research Database (Denmark)

Tuxen, M.K.; Sölétormos, G.; Petersen, P.H.

1999-01-01

biological variation. The aim of the study was to assess (i) the analytical imprecision (CVA) and the average inherent intra- and interindividual biological variation (CVTI and CVG, respectively) for CA 125, CEA, and TPA in a group of healthy women; (ii) the significance of changes in serial results of each...

The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.

Science.gov (United States)

Jiang, H; Chen, S; Li, C; Lu, N; Yue, Y; Yin, Y; Zhang, Y; Zhi, X; Zhang, D; Yuan, Y

2017-04-04

Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA-BDNF pathway in MDD. We examined serum protein concentrations in the tPA-BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA-BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.

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

Acute, massive pulmonary embolism with right heart strain and hypoxia requiring emergent tissue plasminogen activator (TPA infusion

Directory of Open Access Journals (Sweden)

Jonathan Patane

2017-04-01

Full Text Available History of present illness: A 63-year-old male presented to the emergency department with shortness of breath. He had a history of prostate cancer and two previous pulmonary embolisms, but was not currently on blood thinners. He had no associated chest pain at the time of presentation, but endorsed hemoptysis. Vital signs were significant for a heart rate of 88, blood pressure 145/89, oxygen saturation in the mid-70’s on room air which increased to mid-80’s on 15L facemask. His exam was significant for clear lung sounds bilaterally. He immediately underwent chest x-ray which showed no acute abnormalities. A bedside ultrasound was performed which showed evidence of right ventricular and atrial dilation, consistent with right heart strain. Given that the patient’s oxygen saturations improved to 88% on 15L facemask, the patient was felt to be stable enough for CT angiography. Significant findings: CT angiogram showed multiple large acute pulmonary emboli, most significantly in the distal right main pulmonary artery (image 1 and 2. Additional pulmonary emboli were noted in the bilateral lobar, segmental, and subsegmental levels of all lobes. There was a peripheral, wedge-shaped consolidation surrounded by groundglass changes in the posterolateral basal right lower lobe that was consistent with a small lung infarction (image 3. Discussion: The patient underwent in the Emergency Department a tissue plasminogen activator (TPA infusion of alteplase 100 mg over 2 hours for his massive acute pulmonary embolisms. Throughout his TPA infusion his oxygen saturations became improved to mid-90’s and his shortness of breath symptoms began improving. His troponin returned at 0.15 ng/mL, suggesting right heart strain. He was admitted to the ICU for continued monitoring and treatment. An acute, massive pulmonary embolism is described as having more than 50% occlusion of pulmonary blood flow.1 The main causes of hypoxia includes ventilation

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

A family of uranyl-aromatic dicarboxylate (pht-, ipa-, tpa-) framework hybrid materials: photoluminescence, surface photovoltage and dye adsorption.

Science.gov (United States)

Gao, Xue; Wang, Che; Shi, Zhong-Feng; Song, Jian; Bai, Feng-Ying; Wang, Ji-Xiao; Xing, Yong-Heng

2015-07-07

Four uranyl complexes [(UO2)(pht)H2O]·H2O (pht = phthalic acid) (1), (UO2)2(Hipa)4(H2O)2 (Hipa = isophthalic acid) (2), (UO2)(tpa)(DMF)2 (tpa = terephthalic acid) (3) and (UO2)(box)2 (box = benzoic acid) (4) were synthesized by the reaction of UO2(CH3COO)2·2H2O as the metal source and phthalic acid, isophthalic acid, terephthalic acid or benzoic acid as the ligand. They were characterized by elemental analyses, IR, UV-Vis, XRD, single crystal X-ray diffraction analysis and thermal gravimetric analysis. The structural analysis reveals that complex 1 exhibits a one-dimensional chain structure constructed by the building unit [(UO2)2(pht)4(H2O)2] and further extends the chain into a 2D supramolecular architecture by hydrogen bonding interactions. Complex 2 is a discrete [(UO2)2(Hipa)4(H2O)2] structure, and by the hydrogen bonding interaction, forms a 3D supramolecular structure. In complexes 3 and 4, adjacent uranyl polyhedra form a 1D chain through bridging terephthalic acid and benzoic acid, respectively. In order to extend their functional properties, their photoluminescence, surface photovoltage and dye adsorption properties have been studied.

Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo

DEFF Research Database (Denmark)

Wang, Z; Pedersen, Esben Ditlev Kølle; Basse, A

2010-01-01

that Rac1 is essential for DMBA/TPA-induced skin tumor formation. This corresponded to a decreased keratinocyte hyperproliferation, although apoptosis was not detectably altered. Activated Rac1 promoted Erk-dependent hyperproliferation by Pak1-mediated Mek activation independent of Mek1 phosporylation...

The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

Science.gov (United States)

Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay

2016-08-17

Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children. Copyright © 2016 GSK group of companies. Published by Elsevier Ltd.. All rights reserved.

Diagnostic value of combined determination of serum tumor markers (NSE, CA-242, TPA, CEA) levels in patients with lung cancer

International Nuclear Information System (INIS)

Liu Juzhen; Cai Tietie; Qin Shana

2007-01-01

Objective: To investigate the diagnostic value of combined determination of serum NSE, CA242, tissue polypeptide antigen (TPA) and CEA levels in patients with primary lung cancer. Methods: Serum NSE, CA242, TPA and CEA levels were determined with ELISA in (1) 102 patients with various types of primary lung carcinoma (adenocarcinoma 38, squamous cell carcinoma 32, small cell lung carcinoma 32) (2) 33 patients with open lung T. B. and (3) 30 controls. Results: (1) In patients with lung cancer, serum levels of all the four markers were increased and significantly higher than their respective values in patients with open lung T.B. and controls. (2) Positive rate of combined any two markers were 75% for adenocarcinoma, 50% for squamous cell carcinoma and 65% for small cell lung carcinoma, while false positive rate was only 9% for T.B patients and none for the controls. (3) The most appropriate single marker for each specific type of lung cancer was: NSE for SCLC (sensitivity 72%, specificity 97%, CA242 for adenocarcinoma sensitivity 62%, specificity 90%). Conclusion: Combined determination of these tumor markers would improve the sensitivity and specificity for diagnosis of primary lung carcinoma. (authors)

Potentiation of phorbol ester-induced coronary vasoconstriction in dogs following endothelium disruption

International Nuclear Information System (INIS)

Roberts, R.B.; Ku, D.D.

1986-01-01

In the present study, the effect of phorbol ester, 12-0-tetradecanoylphorbol 13-acetate (TPA), activation of protein kinase C on coronary vascular reactivity was studied in isolated dog coronary arteries. Addition of TPA (10-100 nM) produced a slow, time- and dose-dependent contraction reaching a maximum at approx 2-3 hrs and was essentially irreversible upon washing. Disruption of the endothelium(EC) greatly accelerated the development as well as increase the magnitude of TPA contraction (50-100%). Prior treatment of vessels with phentolamine (1μM), cyproheptadine (1μH) and ibuprofen (1μg/ml) did not alter the TPA contraction. Furthermore, in contrast to previously reported calcium-dependence of TPA contraction in other vessels, complete removal of extracellular calcium (Ca 0 ) or addition of 1μM nimodipine after TPA(30nM) resulted in only 32 +/- 4% and 25 +/- 3% reversal of TPA contraction, respectively. Addition of amiloride (10μM to 1mM), however, resulted in a dose-dependent reversal of TPA contraction. The results of the present study indicate that a similar activation of protein kinase C by TPA leads to potent coronary vasoconstriction, which is not completely dependent on Ca 0 . More importantly, these results further support their hypothesis that EC also functions as an inhibitory barrier to prevent circulating vasoconstrictors from exerting their deleterious constrictory effects

Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

DEFF Research Database (Denmark)

Kristiansen, Søren; Jørgensen, Lars Mønster; Høgh Hansen, Morten

2015-01-01

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the ...

Atividade de plasmina e plasminogênio no leite longa vida com alta e baixa contagem de células somáticas durante o armazenamento Activity of plasmin and plasminogen in ultra high temperature milk with high and low somatic cell counts during storage

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Carlos Humberto Corassin

2010-12-01

Full Text Available O objetivo deste estudo foi avaliar o efeito da contagem de células somáticas (CCS do leite na atividade de plasmina e plasminogênio durante o período de armazenamento do leite longa vida integral. Os leites crus foram categorizados em grupos de CCS de baixa (342.000-487.000 células mL-1 e alta contagem (603.000-808.000 células mL-1. Dois lotes de leite longa vida em cada categoria de CCS foram analisados para determinação de plasmina e plasminogênio após 10, 30, 60, 90 e 120 dias de armazenamento em temperatura ambiente. Para a fabricação do leite longa vida, o leite cru foi submetido à pasteurização rápida seguida da esterilização industrial do leite por injeção de vapor pelo método direto e embalagem asséptica do produto. A CCS não apresentou efeitos sobre as características físico-químicas do leite cru, e nem sobre a atividade de plasmina e plasminogênio nos leites cru e longa vida, armazenados por 120 dias. Entretanto, independentemente da CCS, a atividade de plasmina e plasminogênio aumentou no leite longa vida ao longo do armazenamento, indicando a possibilidade de aumento da proteólise no produto durante sua vida de prateleira.This study aimed to evaluate the effect of somatic cell counts (SCC in milk on plasmin and plasminogen activities of ultra high temperature (UHT milk during storage. Raw milks were categorized in SCC groups of low (342,000-487,000 cells mL-1 and high cells (603,000-808,000 cells mL-1. Two replicates of UHT milks within each SCC category were analyzed for plasmin and plasminogen activities after 10, 30, 60, 90 and 120 days of storage at room temperature. For manufacture of UHT milk, raw milk was pasteurized and sterilized by direct vapor injection process, followed by aseptic packaging. SCC had no effect on physical-chemical characteristics of raw milk, and on plasmin or plasminogen activities in raw and UHT milks during 120 days of storage. However, independently of the SCC in raw milk

Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by endogenous plasminogen activator inhibitor-1.

Science.gov (United States)

Deshet, Naamit; Lupu-Meiri, Monica; Espinoza, Ingrid; Fili, Oded; Shapira, Yuval; Lupu, Ruth; Gershengorn, Marvin C; Oron, Yoram

2008-09-01

PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-induced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor 1-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by endogenous uPA is limited by PN's degradation and negatively controlled by endogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists.

New aspects of blood collection and handling procedures for the assessment of t-PA and PAI-1 variables after the introduction of acid blood collection

NARCIS (Netherlands)

Meijer, P.; Kret, R.; Bloetjes, P.T.M.; Rosen, S.; Kluft, C.

1994-01-01

Blood collection and handling procedures for t-PA activity have thusfar been rather strict and have restrained the use in clinical practice. We evaluated simplifications in the procedures for specifically the use of Stabilyte® vacutainers with respect to time before centrifugation of blood, storage

Biochemical studies of the differentiation of HL-60 cells into monocytes by either IFN, VIT, D3 or TPA

International Nuclear Information System (INIS)

Miyamoto, S.; Whyzmuzis, C.; Oronsky, B.; Wu, J.M.

1987-01-01

The authors have studied the differentiation process of the human promyelocytic cell line, HL-60, by treatment of these cells with either gamma interferon, 1, 25 dihydroxyvitamin D 3 or a phorbol ester, TPA. The cells were grown in RPMI 1640, 10% FCS with each respective agent, then pulsed labeled with 35 S-Met, harvested, lysed and subfractionated by centrifugation into post-ribosomal and ribosomal salt was fractions (RSW). These fractions were examined by SDS gel electrophoresis. The culture supernatant from the treated cells was dialyzed and passed over a heparin agarose affinity column. The absorbed material was eluted from the column by a step-wise salt gradient and analyzed by SDS gel electrophoresis. They have also observed that in a rabbit reticulocyte lysate assay, the RSW from control cells show inhibition of protein synthesis. The RSW from cells treated with either high concentrations (200-1000 units/ml) of gamma interferon, Vit D 3 or TPA did not show this inhibition. Some possible explanations for this phenomenon are the loss or inactivation of a component necessary for protein synthesis which is triggered by differentiation, or the differentiation-related modulation of translational inhibitor(s). They have used FPLC to further analyze the RSW, but because the factor(s) are present in such small quantities further analytical and more sensitive procedures need to be pursued

Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells.

Science.gov (United States)

Lin, Feng-Yan; Hsieh, Yi-Hsien; Yang, Shun-Fa; Chen, Chang-Tai; Tang, Chih-Hsin; Chou, Ming-Yung; Chuang, Yi-Ting; Lin, Chiao-Wen; Chen, Mu-Kuan

2015-10-01

Naturally occurring agents, such as resveratrol, have been determined to benefit health. Numerous studies have demonstrated that resveratrol has antioxidative, cardioprotective, and neuroprotective properties. However, the effect of resveratrol exerts on the metastasis of oral cancer cells remains unclear. In this study, we investigated the effect the anti-invasive activity of resveratrol on a human oral cancer cell line (SCC-9) in vitro and the underlying mechanisms. Cell viability was examined by MTT assay, whereas cell motility was measured by migration and wound-healing assays. Zymography, reverse-transcriptase polymerase chain reaction (PCR), and promoter assays confirmed the inhibitory effects of resveratrol on matrix metalloproteinase-9 (MMP-9) expression in oral cancer cells. We established that various concentrations (0-100 μM) of resveratrol inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration capacities of SCC-9 cells and caused no cytotoxic effects. Zymography and Western blot analyses suggested that resveratrol inhibited TPA-induced MMP-9 gelatinolytic activity and protein expression. In addition, the results indicated that resveratrol inhibited the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 and extracellular-signal-regulated kinase (ERK)1/2 involved in downregulating protein expression and the transcription of MMP-9. In summary, resveratrol inhibited MMP-9 expression and oral cancer cell metastasis by downregulating JNK1/2 and ERK1/2 signals pathways and, thus, exerts beneficial effects in chemoprevention. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Secretion of alpha 2-plasmin inhibitor is impaired by amino acid deletion in a small region of the molecule.

Science.gov (United States)

Toyota, S; Hirosawa, S; Aoki, N

1994-02-01

Alpha 2-plasmin inhibitor (alpha 2PI) deficiency Okinawa results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of the deletion of Glu137 in the amino acid sequence of alpha 2PI. To examine the effects of replacing the amino acid occupying position 137 or deleting its neighboring amino acid on alpha 2PI secretion, we used oligonucleotide-directed mutagenesis of alpha 2PI cDNA to change the codon specifying Glu137 or delete a codon specifying its neighboring amino acid. The effects were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of media from transiently transfected COS-7 cells. Replacement of Glu137 with an amino acid other than Cys had little effect on alpha 2PI secretion. In contrast, deletion of an amino acid in a region spanning a sequence of less than 30 amino acids including positions 127 and 137 severely impaired the secretion. The results suggest that structural integrity of the region, rather than its component amino acids, is important for the intracellular transport and secretion of alpha 2PI.

Purification of a peptide from seahorse, that inhibits TPA-induced MMP, iNOS and COX-2 expression through MAPK and NF-kappaB activation, and induces human osteoblastic and chondrocytic differentiation.

Science.gov (United States)

Ryu, BoMi; Qian, Zhong-Ji; Kim, Se-Kwon

2010-03-30

Ongoing efforts to search for naturally occurring, bioactive substances for the amelioration of arthritis have led to the discovery of natural products with substantial bioactive properties. The seahorse (Hippocampus kuda Bleeler), a telelost fish, is one source of known beneficial products, yet has not been utilized for arthritis research. In the present work, we have purified and characterized a bioactive peptide from seahorse hydrolysis. Among the hydrolysates tested, pronase E-derived hydrolysate exhibited the highest alkaline phosphatase (ALP) activity, a phenotype marker of osteoblast and chondrocyte differentiation. After its separation from the hydrolysate by several purification steps, the peptide responsible for the ALP activity was isolated and its sequence was identified as LEDPFDKDDWDNWK (1821Da). We have shown that the isolated peptide induces differentiation of osteoblastic MG-63 and chondrocytic SW-1353 cells by measuring ALP activity, mineralization and collagen synthesis. Our results indicate that the peptide acts during early to late stages of differentiation in MG-63 and SW-1353 cells. We also assessed the concentration dependence of the peptide's inhibition of MMP (-1, -3 and -13), iNOS and COX-2 expression after treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), a common form of phorbol ester. The peptide also inhibited NO production in MG-63 and SW-1353 cells. To elucidate the mechanisms by which the peptide acted, we examined its effects on TPA-induced MAPKs/NF-kappaB activation and determined that the peptide treatment significantly reduced p38 kinase/NF-kappaB in MG-63 cells and MAPKs/NF-kappaB in SW-1353 cells.

The test ability of fish Tawes to leachate garbage dump (TPA) Benowo

Science.gov (United States)

Juliardi AR, N. R.; Wiyanti, R. I.

2018-01-01

Leachate is a liquid from waste containing elements of dissolved and suspended elements. Garbage collected at the landfill site contains organic, inorganic and heavy metal substances. If the rains will produce leachate with mineral content, organic and heavy metals. When the condition or leachate flow in let to the soil surface can cause negative effects to the surrounding environment including for humans. Toxicity test it was conducted to determine the level of leachate toxicity of the test animals living in surface water located around of the “TPA Benowo”. In this study using Tawes fish with length between 4-6 cm. In this toxicity test is done in 2 stages, namely: range finding test, the search for this range is obtained 0% concentrations (as control) 0,3%; 0,6%; 0,9%; 0,12% and 0,15%. The next stage of toxicity acute test, at this stage of toxicity concentration do smaller again that is: 0,18%; 0,36%; 0,54%; 0,72% and 0,9%. The results obtained LC50 value of 0,385%, while eyes, brown stomach skin.

Functional cooperativity between two TPA responsive elements in undifferentiated F9 embryonic stem cells.

Science.gov (United States)

Okuda, A; Imagawa, M; Sakai, M; Muramatsu, M

1990-01-01

We have recently identified an enhancer, termed GPEI, in the 5'-flanking region of the rat glutathione transferase P gene, that is composed of two imperfect TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive elements (TREs). Unlike other TRE-containing enhancers, GPEI exhibits a strong transcriptional enhancing activity in F9 embryonic stem cells. Mutational analyses have revealed that the high activity of GPEI is mediated by two imperfect TREs. Each TRE-like sequence has no activity by itself but acts synergistically to form a strong enhancer which is active even in the very low level of AP-1 activity in F9 cells. Furthermore, we show that synthetic DNAs containing two perfect TREs in certain arrangements have strong transcriptional enhancing activities in F9 cells and the activity is greatly influenced by the relative orientation and the distance of two TREs. Images Fig. 1. Fig. 2. Fig. 3. PMID:2323334

Variation in the activities of late stage filaggrin processing enzymes, calpain-1 and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels, corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed facial stratum corneum of different ethnicities.

Science.gov (United States)

Raj, N; Voegeli, R; Rawlings, A V; Summers, B; Munday, M R; Lane, M E

2016-12-01

Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and corneocyte maturation. Enzyme activities, PCA levels and corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature corneocytes. Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest

Software for a magnetic dick drive unit connected with a computer TPA-1001-i

International Nuclear Information System (INIS)

Elizarov, O.I.; Mateeva, A.; Salamatin, I.M.

1977-01-01

The disk drive unit with capacity 1250 K and minimal addressing part of memory 1 sector (128 10 -12-bit words) is connected with a TPA-1001-i computer. The operation regimes of the controller, functions and formats of the commands used are described as well as the software. The data transfer between the computer and magnetic disk drive unit is realized by means of programs relocatable in a binary form. These are inserted in a standard program library with modular structure. The manner of control handling and data transfer betweeen programs stored in the library on a magnetic disk drive are described. The resident program (100sub(8) words) inserted in a monitor takes into account special features of the disk drive unit being used. The algorithms of correction programs for a disk drive unit, programs for rewriting the library from papertape to disk drive unit and of the program for writing and reading the monitor are described

Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count.

Science.gov (United States)

Stępień, Ewa; Gruszczyński, Krzysztof; Kapusta, Przemysław; Kowalik, Artur; Wybrańska, Iwona

2015-01-01

Centrifugation is an essential step for plasma preparation to remove residual elements in plasma, especially platelets and platelet-derived microparticles (PMPs). Our working hypothesis was that centrifugation as a preanalytical step may influence some coagulation parameters. Healthy young men were recruited (N=17). For centrifugation, two protocols were applied: (A) the first centrifugation at 2500xg for 15 min and (B) at 2500xg for 20 min at room temperature with a light brake. In protocol (A), the second centrifugation was carried out at 2500xg for 15 min, whereas in protocol (B), the second centrifugation involved a 10 min spin at 13,000 x g. Thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes concentrations were determined by enzyme-linked immunosorbent assays. PMPs were stained with CD41 antibody and annexin V, and analyzed by flow cytometry method. Procoagulant activity was assayed by the Calibrated Automated Thrombogram method as a slope of thrombin formation (CAT velocity). Median TAT and PAP concentrations did not differ between the centrifugation protocols. The high speed centrifugation reduced the median (IQR) PMP count in plasma from 1291 (841-1975) to 573 (391-1010) PMP/µL (P=0.001), and CAT velocity from 2.01 (1.31-2.88) to 0.97 (0.82-1.73) nM/min (P=0.049). Spearman's rank correlation analysis showed correlation between TAT and PMPs in the protocol A plasma which was (rho=0.52, PCentrifugation protocols do not influence the markers of plasminogen (PAP) and thrombin (TAT) generation but they do affect the PMP count and procoagulant activity.

Quantum molecular dynamics simulations of the thermophysical properties of shocked liquid ammonia for pressures up to 1.3 TPa.

Science.gov (United States)

Li, Dafang; Zhang, Ping; Yan, Jun

2013-10-07

We investigate via quantum molecular-dynamics simulations the thermophysical properties of shocked liquid ammonia up to the pressure 1.3 TPa and temperature 120,000 K. The principal Hugoniot is predicted from the wide-range equation of state, which agrees well with the available experimental measurements up to 64 GPa. Our systematic study of the structural properties demonstrates that the liquid ammonia undergoes a gradual phase transition along the Hugoniot. At about 4800 K, the system transforms into a metallic, complex mixture state consisting of NH3, N2, H2, N, and H. Furthermore, we discuss the implications for the interiors of Uranus and Neptune.

Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

Directory of Open Access Journals (Sweden)

Søren Kristiansen

2015-01-01

Full Text Available The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.

Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer.

Science.gov (United States)

Kristiansen, Søren; Jørgensen, Lars Mønster; Hansen, Morten Høgh; Nielsen, Dorte; Sölétormos, György

2015-01-01

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.

Thickness-dependent nonlinear optical properties of CsPbBr3 perovskite nanosheets.

Science.gov (United States)

Zhang, Jun; Jiang, Tian; Zheng, Xin; Shen, Chao; Cheng, Xiang'ai

2017-09-01

Halide perovskite has attracted significant attention because of excellent optical properties. Here, we study the optical properties of CsPbBr 3 perovskite nanosheets and observe that the nonlinear optical properties can be tuned by the thickness. The photoluminescence (PL) properties and nonlinear absorption effects induced by saturation absorption (SA) and two-photon absorption (TPA) in CsPbBr 3 nanosheets with different thicknesses (from 104.6 to 195.4 nm) have been studied. The PL intensity increases nearly three times with changing from the thinnest one to the thinnest under the same excitation condition. Moreover, the same phenomenon takes place no matter when SA or TPA effects happen. The PL lifetime (τ) varies inversely with the thickness. When SA happens, τ decreases from 11.54 to 9.43 ns while when TPA happens new decay channels emerge with the increase of the thickness. Besides, both saturation intensity (I sat ) and the modulation depth are proportional to the thickness (I sat rises from 3.12 to 4.79  GW/cm 2 , the modulation depth increases from 18.6% to 32.3%), while the TPA coefficient (β) is inversely proportional with the thickness (decreases from 10.94 to 4.73  cm/GW). In addition, quantum yields and thicknesses are in the direct ratio. This Letter advocates great promise for nonlinear optical property related photonics devices.

Pengaruh Parameter Fisika dan Mikrobiologi Leachet terhadap Kesehatan Lingkungan di TPA Muara Fajar Rumbai Pekanbaru

Directory of Open Access Journals (Sweden)

Riski Novera Yenita

2015-11-01

Full Text Available Secara umum kondisi sampah kota memperlihatkan karakteristik yang khas. Kondisi sampah kota memiliki komposisi terbesar sampah organik dengan nilai rata-rata 79,164%, sedangkan sampah anorganik hanya sebesar 20,836%. Jenis penelitian ini adalah metode survey, dimana TPA Muara Fajar Pekanbaru dijadikan lokasi pengambilan sampel. Sampel yang diambil kemudian dianalisis kadar fisika dan biologi leachet di laboratorium, selanjutnya data yang didapat dilakukan analisis secara deskriptif sesuai dengan SNI 06-2412-1991. Sumber data penelitian yaitu wawancara, observasi dan pemeriksaan laboratorium. Dua kode sampel pada air lindi didapatkan hasil analisis bahwa pada kode sampel I dan II suhu yang didapatkan adalah 25oC. TSS pada kode sampel I didapatkan hasil sebesar 70 mg/l dan kode sampel II 190 mg/l. pH pada kode sampel I dan II didapatkan hasil sebesar 8, sedangkan untuk kadar E.Coli pada kode sampel I dan II didapatkan hasil tidak terhingga. 

Interpretation of sequential measurements of cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer

DEFF Research Database (Denmark)

Tuxen, Malgorzata K.; Sölétormos, G; Petersen, P H

2001-01-01

The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer patie...

HIF-2alpha-dependent PAI-1 induction contributes to angiogenesis in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Geis, Theresa, E-mail: geis@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Döring, Claudia, E-mail: C.Doering@em.uni-frankfurt.de [Dr. Senckenberg Institute of Pathology, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Popp, Rüdiger, E-mail: popp@vrc.uni-frankfurt.de [Institute for Vascular Signalling, Centre for Molecular Medicine, Faculty of Medicine Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main (Germany); Grossmann, Nina, E-mail: grossmann@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Fleming, Ingrid, E-mail: fleming@vrc.uni-frankfurt.de [Institute for Vascular Signalling, Centre for Molecular Medicine, Faculty of Medicine Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main (Germany); Hansmann, Martin-Leo, E-mail: m.l.hansmann@em.uni-frankfurt.de [Dr. Senckenberg Institute of Pathology, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Dehne, Nathalie, E-mail: dehne@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Brüne, Bernhard, E-mail: b.bruene@biochem.uni-frankfurt.de [Institute of Biochemistry I—Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

2015-02-01

Hypoxia promotes progression of hepatocellular carcinoma (HCC), not only affecting tumor cell proliferation and invasion, but also angiogenesis and thus, increasing the risk of metastasis. Hypoxia inducible factors (HIF)-1α and -2α cause adaptation of tumors to hypoxia, still with uncertainties towards the angiogenic switch. We created a stable knockdown of HIF-1α and HIF-2α in HepG2 cells and generated cocultures of HepG2 spheroids with embryonic bodies as an in vitro tumor model mimicking the cancer microenvironment. The naturally occuring oxygen and nutrient gradients within the cocultures allow us to question the role of distinct HIF isoforms in regulating HCC angiogenesis. In cocultures with a HIF-2α knockdown, angiogenesis was attenuated, while the knockdown of HIF-1α was without effect. Microarray analysis identified plasminogen activator inhibitor 1 (PAI-1) as a HIF-2α target gene in HepG2 cells. The knockdown of PAI-1 in HepG2 cells also lowered angiogenesis. Blocking plasmin, the downstream target of PAI-1, with aprotinin in HIF-2α knockdown (k/d) cells proved a cause–effect relation and restored angiogenesis, with no effect on control cocultures. Suggestively, HIF-2α increases PAI-1 to lower concentrations of active plasmin, thereby supporting angiogenesis. We conclude that the HIF-2α target gene PAI-1 favors the angiogenic switch in HCC. - Highlights: • HepG2 were cocultured with stem cells to mimic a cancer microenvironment in vitro. • A knockdown of HIF-2α reduces angiogenesis. • PAI-1 was identified as a HIF-2α target gene in HCC by microarray analysis. • HIF-2α induces the angiogenic switch via inhibition of plasmin.

HIF-2alpha-dependent PAI-1 induction contributes to angiogenesis in hepatocellular carcinoma

International Nuclear Information System (INIS)

Geis, Theresa; Döring, Claudia; Popp, Rüdiger; Grossmann, Nina; Fleming, Ingrid; Hansmann, Martin-Leo; Dehne, Nathalie; Brüne, Bernhard

2015-01-01

Hypoxia promotes progression of hepatocellular carcinoma (HCC), not only affecting tumor cell proliferation and invasion, but also angiogenesis and thus, increasing the risk of metastasis. Hypoxia inducible factors (HIF)-1α and -2α cause adaptation of tumors to hypoxia, still with uncertainties towards the angiogenic switch. We created a stable knockdown of HIF-1α and HIF-2α in HepG2 cells and generated cocultures of HepG2 spheroids with embryonic bodies as an in vitro tumor model mimicking the cancer microenvironment. The naturally occuring oxygen and nutrient gradients within the cocultures allow us to question the role of distinct HIF isoforms in regulating HCC angiogenesis. In cocultures with a HIF-2α knockdown, angiogenesis was attenuated, while the knockdown of HIF-1α was without effect. Microarray analysis identified plasminogen activator inhibitor 1 (PAI-1) as a HIF-2α target gene in HepG2 cells. The knockdown of PAI-1 in HepG2 cells also lowered angiogenesis. Blocking plasmin, the downstream target of PAI-1, with aprotinin in HIF-2α knockdown (k/d) cells proved a cause–effect relation and restored angiogenesis, with no effect on control cocultures. Suggestively, HIF-2α increases PAI-1 to lower concentrations of active plasmin, thereby supporting angiogenesis. We conclude that the HIF-2α target gene PAI-1 favors the angiogenic switch in HCC. - Highlights: • HepG2 were cocultured with stem cells to mimic a cancer microenvironment in vitro. • A knockdown of HIF-2α reduces angiogenesis. • PAI-1 was identified as a HIF-2α target gene in HCC by microarray analysis. • HIF-2α induces the angiogenic switch via inhibition of plasmin

Assessment of plasminogen synthesis in vitro by mouse tumor cells using a competition radioimmunoassay for mouse plasminogen

International Nuclear Information System (INIS)

Roblin, R.O.; Bell, T.E.; Young, P.L.

1978-01-01

A sensitive, specific competition radioimmunoassay for mouse plasmin(ogen) has been developed in order to determine whether mouse tumor cells can synthesize plasminogen in vitro. The rabbit anti-BALB/c mouse plasminogen antibodies used in the assay react with the plasminogen present in serum from BALB/c, C3H, AKR and C57BL/6 mice, and also recognized mouse plasmin. The competition radiommunoassay can detect as little as 50 ng of mouse plasminogen. No competition was observed with preparations of fetal calf, human and rabbit plasminogens. A variety of virus-transformed and mouse tumor cell lines were all found to contain less than 100 ng mouse plasminogen/mg of cell extract protein. Thus, if the plasminogen activator/plasmin system is important in the growth or movement of this group of tumor cells, the cells will be dependent upon the circulatory system of the host for their plasminogen supply. (Auth.)

Operating experience of the TPA-1001 mini-computer in experimental control systems of main synchrophasotron parameters

International Nuclear Information System (INIS)

Kazanskij, G.S.; Khoshenko, A.A.

1978-01-01

The experience of application of a Mini-computer, TPA-1001 to control the basic parameters of a synchrophasotron is discussed. The available data have shown that the efficiency of a computer management and measurement system (CMMS) for an accelerator can be determined as a trade-off between the accelerator and the system reliability, and betWeen the system mobility and its softWare. At present, the system employs two VT-340 display units, an arithmetic unit and an accelerating frequency measurement loop. In addition, the system memory is expanded up to 12 K. A new interactive program has been developed which enables the user to interact with the system Via three units (a teletype and two display units). An accelerating frequency measuring and control flowchart has been implemented and covers the whole duty cycle, while its measuring accuracy is better than 4x10 -4

Activation of pro-urokinase and plasminogen on human sarcoma cells

DEFF Research Database (Denmark)

Stephens, R W; Pöllänen, J; Tapiovaara, H

1989-01-01

from the cells with tranexamic acid, an analogue of lysine. The bound plasmin was the result of plasminogen activation on the cell surface; plasmin activity was not taken up onto cells after deliberate addition of plasmin to the serum-containing medium. The cell surface plasmin formation was inhibited...

Topical anti-inflammatory activity of Calea prunifolia HBK (Asteraceae) in the TPA model of mouse ear inflammation

International Nuclear Information System (INIS)

Gomez, Milton; Gil, Juan F.

2011-01-01

Phytochemical study of Calea prunifolia HBK identified two compounds derived from p-hydroxyacetophenone, the 1-(2-hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2.en-1-one showed a satisfactory anti-inflammatory activity (58.33%), when considering that this is a natural product. Although the two derived compounds are structurally similar, the anti-inflammatory activity of 1-(2-hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one was not significant (2.08%). The test was conducted in a model of inflammation induced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in the ear of mice. The positive control was tested with indomethacin and the negative control was done only with vehicle. These results allow the identification of a pharmacophore group that through molecular modeling studies and organic synthesis can result in compounds with improved anti-inflammatory activity. (author)

Topical anti-inflammatory activity of Calea prunifolia HBK (Asteraceae) in the TPA model of mouse ear inflammation

Energy Technology Data Exchange (ETDEWEB)

Gomez, Milton; Gil, Juan F., E-mail: miltongoba@uniquindio.edu.co [Grupo de Busqueda de Principios Bioactivos, Programa de Quimica, Universidad del Quindio, Armenia (Colombia)

2011-09-15

Phytochemical study of Calea prunifolia HBK identified two compounds derived from p-hydroxyacetophenone, the 1-(2-hydroxy-5-(1-methoxyethyl)phenyl)-3-methylbut-2.en-1-one showed a satisfactory anti-inflammatory activity (58.33%), when considering that this is a natural product. Although the two derived compounds are structurally similar, the anti-inflammatory activity of 1-(2-hydroxy-5-methoxyphenyl)-3-methylbut-2-en-1-one was not significant (2.08%). The test was conducted in a model of inflammation induced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in the ear of mice. The positive control was tested with indomethacin and the negative control was done only with vehicle. These results allow the identification of a pharmacophore group that through molecular modeling studies and organic synthesis can result in compounds with improved anti-inflammatory activity. (author)

Calcium permeability of the T lymphocyte plasma membrane: counteraction of phorbol ester and A23187

Energy Technology Data Exchange (ETDEWEB)

Csermely, P.; Szamel, M.; Somogyi, J.

1986-01-01

The intracellular calcium concentration (Ca/sub i/) of T lymphocytes was measured using the fluorescent indicator quin2. Different ionophores effectively enhanced the Ca permeability of the plasma membrane. The effective concentration of the ionophores required for permeabilization increased in the order of ionomycin, A23187 and X537-A (lasalocid-A). 12-0-tetradecanoyl-phorbol-13-acetate (TPA) in submicromolar concentrations did not change Ca/sub i/. The addition of TPA immediately before the A23187-permeabilization did not alter the Ca ionophoretic effect of A23187. However, prolonged incubation with TPA decreased the efficiency of A23187 permeabilizing the plasma membrane for calcium ions. This effect was concentration and time dependent, being maximal at TPA concentrations higher than 10 nM with a preincubation time of 1.5 hours. TPA induced relative A23187 insensitivity is most probably not due to a direct effect of TPA on the ionophore as it is concentration and time dependent. Moreover the fluorescence and fluorescence polarization of A23187 as well as the energy transfer between the tryptophan groups of the membrane proteins and A23187 showed no significant change during incubation with TPA. These results indicate that membrane fluidity changes or A23187 immobilization also do not play a prominent role in the explanation of the phenomenon. However the supposed intracellular heavy metal content of T lymphocyte might be a possible source of the TPA induced relative insensitization towards A23187.

Physical determinants of fibrinolysis in single fibrin fibers.

Directory of Open Access Journals (Sweden)

Igal Bucay

Full Text Available Fibrin fibers form the structural backbone of blood clots; fibrinolysis is the process in which plasmin digests fibrin fibers, effectively regulating the size and duration of a clot. To understand blood clot dissolution, the influence of clot structure and fiber properties must be separated from the effects of enzyme kinetics and perfusion rates into clots. Using an inverted optical microscope and fluorescently-labeled fibers suspended between micropatterned ridges, we have directly measured the lysis of individual fibrin fibers. We found that during lysis 64 ± 6% of fibers were transected at one point, but 29 ± 3% of fibers increase in length rather than dissolving or being transected. Thrombin and plasmin dose-response experiments showed that the elongation behavior was independent of plasmin concentration, but was instead dependent on the concentration of thrombin used during fiber polymerization, which correlated inversely with fiber diameter. Thinner fibers were more likely to lyse, while fibers greater than 200 ± 30 nm in diameter were more likely to elongate. Because lysis rates were greatly reduced in elongated fibers, we hypothesize that plasmin activity depends on fiber strain. Using polymer physics- and continuum mechanics-based mathematical models, we show that fibers polymerize in a strained state and that thicker fibers lose their prestrain more rapidly than thinner fibers during lysis, which may explain why thick fibers elongate and thin fibers lyse. These results highlight how subtle differences in the diameter and prestrain of fibers could lead to dramatically different lytic susceptibilities.

Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice.

Science.gov (United States)

Nakajima, Jun'ichi; Nakae, Dai; Yasukawa, Ken

2013-08-01

Whether and how synthetic cannabinoids affect inflammation and carcinogenesis has not been well studied. The present study was thus conducted to assess effects of synthetic cannabinoids on inflammation and carcinogenesis in vivo in mice. Twenty-three analogues of synthetic cannabinoids were isolated from, and identified as adulterants in, illegal drugs distributed in the Tokyo metropolitan area, and were examined for their inhibitory effects on the induction of oedema in mouse ears by 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, selected cannabinoids, JWH-018, -122 and -210, were studied for their effects on carcinogenesis induced in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by TPA. Among cannabinoids, naphthoylindoles mostly exhibited superior inhibitory effects against TPA-induced ear oedema and, especially, JWH-018, -122 and -210 showed potent activity with 50% inhibitory dose (ID50) values of 168, 346 and 542 nm, respectively (an activity corresponding to that of indometacin (ID50 = 908 nm)). Furthermore these three compounds also markedly suppressed the tumour-promoting activity of TPA. This is the first report indicating the structure-activity relationships for the anti-inflammatory activity of synthetic cannabinoids on TPA-induced inflammation in mice. Naphthoylindoles, JWH-018, -122 and -210, had the most potent anti-inflammatory activity and also markedly inhibited tumour promotion by TPA in the two-stage mouse skin carcinogenesis model. The present results suggest that synthetic cannabinoids, such as JWH-018, -122 and -210, may be used as cancer chemopreventive agents in the future. © 2013 Royal Pharmaceutical Society.

Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

Science.gov (United States)

Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

2015-04-01

Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet.

Isolation and characterization of human glycophorin A cDNAs using a synthetic oligonucleotide approach: nucleotide sequence, mRNA structure and regulation by 12-O-tetradecanoylphorbol 13-acetate (TPA)

International Nuclear Information System (INIS)

Siebert, P.D.; Fukuda, M.

1986-01-01

The authors have previously shown that treatment of human erythroleukemic K562 cells with the tumor-promoting phorbol ester, TPA, results in a diminished expression of glycophorin A at the level of protein biosynthesis and in vitro mRNA translation activity. To further examine the structure, relationships and expression of human glycophorins they have successfully isolated and sequenced several glycophorin A specific cDNA clones derived from K562 cells, by making extensive use of mixed and exact synthetic oligonucleotides as primers and radioactively labeled probes. The nucleotide sequence obtained from the largest glycophorin A cDNA suggests the presence of a hydrophobic leader-like peptide of at least 19 amino acids. Northern gel analysis using both whole cDNA-plasmid and synthetic oligonucleotide probes revealed the existence of multiple mRNAs, three of which they believe to be glycophorin A-specific, whereas a fourth and smaller mRNA appears to be glycophorin B-specific. Furthermore, the abundance of all four glycophorin mRNAs were found to be extensively reduced following treatment of K562 cells with TPA suggesting coordinate regulation, possibly at the level of gene transcription

Photodynamic therapy using a novel irradiation source, LED lamp, is similarly effective to photodynamic therapy using diode laser or metal-halide lamp on DMBA- and TPA-induced mouse skin papillomas.

Science.gov (United States)

Takahashi, Hidetoshi; Nakajima, Susumu; Ogasawara, Koji; Asano, Ryuji; Nakae, Yoshinori; Sakata, Isao; Iizuka, Hajime

2014-08-01

Photodynamic therapy (PDT) is useful for superficial skin tumors such as actinic keratosis and Bowen disease. Although PDT is non-surgical and easily-performed treatment modality, irradiation apparatus is large and expensive. Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-ο-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model, we compared the efficacy of TONS501- and ALA-PDT with a LED lamp, a diode laser lamp or a metal-halide lamp on the skin tumor regression. TONS501-PDT using 660 nm LED lamp showed anti-tumor effect at 1 day following the irradiation and the maximal anti-tumor effect was observed at 3 days following the irradiation. There was no significant difference in the anti-tumor effects among TONS501-PDT using LED, TONS501-PDT using diode laser, and 5-aminolevulinic acid hydrochloride (ALA)-PDT using metal-halide lamp. Potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma was observed by TONS501-PDT using 660 nm LED, which might be more useful for clinical applications. © 2014 Japanese Dermatological Association.

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

International Nuclear Information System (INIS)

Simian, Marina; Hirai, Yohei; Navre, Marc; Werb, Zena; Lochter, Andre; Bissell, Mina J.

2002-01-01

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

2002-03-06

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

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

Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning

Science.gov (United States)

Seeds, Nicholas W.; Williams, Brian L.; Bickford, Paula C.

1995-12-01

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.

Lattice stability and high-pressure melting mechanism of dense hydrogen up to 1.5 TPa

KAUST Repository

Geng, Hua Y.

2015-09-01

© 2015 American Physical Society. Lattice stability and metastability, as well as melting, are important features of the physics and chemistry of dense hydrogen. Using ab initio molecular dynamics (AIMD), the classical superheating limit and melting line of metallic hydrogen are investigated up to 1.5 TPa. The computations show that the classical superheating degree is about 100 K, and the classical melting curve becomes flat at a level of 350 K when beyond 500 GPa. This information allows us to estimate the well depth and the potential barriers that must be overcome when the crystal melts. Inclusion of nuclear quantum effects (NQE) using path integral molecular dynamics (PIMD) predicts that both superheating limit and melting temperature are lowered to below room temperature, but the latter never reaches absolute zero. Detailed analysis indicates that the melting is thermally activated, rather than driven by pure zero-point motion (ZPM). This argument was further supported by extensive PIMD simulations, demonstrating the stability of Fddd structure against liquefaction at low temperatures.

Blood brain barrier permeability and tPA-mediated neurotoxicity

Science.gov (United States)

Nassar, Taher; Yarovoi, Sergey; Rayan, Anwar; Lamensdorf, Itschak; Karakoveski, Michael; Vadim, Polianski; Fanne, Rami Abu; Jamal, Mahmud; Cines, Douglas B.; Higazi, Abd Al-Roof

2015-01-01

Tissue type plasminogen activator (tPA) induces neuronal apoptosis, disrupt the blood-brain-barrier (BBB), and promotes dilation of the cerebral vasculature. The timing, sequence and contributions of these and other deleterious effects of tPA and their contribution to post-ischemic brain damage after stroke, have not been fully elucidated. To dissociate the effects of tPA on BBB permeability, cerebral vasodilation and protease-dependent pathways, we developed several tPA mutants and PAI-1 derived peptides constructed by computerized homology modeling of tPA. Our data show that intravenous administration of human tPA to rats increases BBB permeability through a non-catalytic process, which is associated with reversible neurotoxicity, brain damage, edema, mortality and contributes significantly to its brief therapeutic window. Furthermore, our data show that inhibiting the effect of tPA on BBB function without affecting its catalytic activity, improves outcome and significantly extends its therapeutic window in mechanical as well as thromboembolic models of stroke. PMID:20060006

Novel model of direct and indirect cost-benefit analysis of mechanical embolectomy over IV tPA for large vessel occlusions: a real-world dollar analysis based on improvements in mRS.

Science.gov (United States)

Mangla, Sundeep; O'Connell, Keara; Kumari, Divya; Shahrzad, Maryam

2016-01-20

Ischemic strokes result in significant healthcare expenditures (direct costs) and loss of quality-adjusted life years (QALYs) (indirect costs). Interventional therapy has demonstrated improved functional outcomes in patients with large vessel occlusions (LVOs), which are likely to reduce the economic burden of strokes. To develop a novel real-world dollar model to assess the direct and indirect cost-benefit of mechanical embolectomy compared with medical treatment with intravenous tissue plasminogen activator (IV tPA) based on shifts in modified Rankin scores (mRS). A cost model was developed including multiple parameters to account for both direct and indirect stroke costs. These were adjusted based upon functional outcome (mRS). The model compared IV tPA with mechanical embolectomy to assess the costs and benefits of both therapies. Direct stroke-related costs included hospitalization, inpatient and outpatient rehabilitation, home care, skilled nursing facilities, and long-term care facility costs. Indirect costs included years of life expectancy lost and lost QALYs. Values for the model cost parameters were derived from numerous resources and functional outcomes were derived from the MR CLEAN study as a reflective sample of LVOs. Direct and indirect costs and benefits for the two treatments were assessed using Microsoft Excel 2013. This cost-benefit model found a cost-benefit of mechanical embolectomy over IV tPA of $163 624.27 per patient and the cost benefit for 50 000 patients on an annual basis is $8 181 213 653.77. If applied widely within the USA, mechanical embolectomy will significantly reduce the direct and indirect financial burden of stroke ($8 billion/50 000 patients). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Acceptor number-dependent ultrafast photo-physical properties of push-pull chromophores using time-resolved methods

Science.gov (United States)

Chi, Xiao-Chun; Wang, Ying-Hui; Gao, Yu; Sui, Ning; Zhang, Li-Quan; Wang, Wen-Yan; Lu, Ran; Ji, Wen-Yu; Yang, Yan-Qiang; Zhang, Han-Zhuang

2018-04-01

Three push-pull chromophores comprising a triphenylamine (TPA) as electron-donating moiety and functionalized β-diketones as electron acceptor units are studied by various spectroscopic techniques. The time-correlated single-photon counting data shows that increasing the number of electron acceptor units accelerates photoluminescence relaxation rate of compounds. Transient spectra data shows that intramolecular charge transfer (ICT) takes place from TPA units to β-diketones units after photo-excitation. Increasing the number of electron acceptor units would prolong the generation process of ICT state, and accelerate the excited molecule reorganization process and the relaxation process of ICT state.

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.

The light-induced spin transition of tetranuclear spin crossover complex [Fe4(CN)4(bpy)4(tpa)2](PF6)4

International Nuclear Information System (INIS)

Nishihara, T; Tanaka, K; Nihei, M; Oshio, H

2009-01-01

We report on the light induced spin transition in the tetranuclear spin crossover complex [Fe 4 (CN) 4 (bpy) 4 (tpa) 2 ](PF 6 ) 4 . The photo-conversion occurs at the specific site (Fe2) of four Fe II ions. The red light irradiation (1.79 eV) gives rise to full conversion of Fe2 into the high spin state from the low spin state. The green light irradiation (2.33 eV) can convert only the half of Fe2 into the high spin state, though the photo-conversion rate in the beginning is much higher than that with the red light. We present a simple model in which the photo-conversion kinetics is controlled by a large background absorption due to remaining three Fe II ions (Fe1, Fe3 and Fe4).

PERANCANGAN PEMBANGKIT LISTRIK TENAGA SAMPAH ORGANIK ZERO WASTE DI KABUPATEN TEGAL (STUDI KASUS DI TPA PENUJAH KABUPATEN TEGAL

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Abdul Muiz Liddinillah Sanfiyan

2017-12-01

Full Text Available Permasalahan sistem pengolahan sampah yang ada di Kabupaten Tegal adalah masih menggunakan sistem Open Dumping. Berdasarkan data yang diperoleh dari Badan Pusat Statistik (BPS Kabupaten Tegal pada tahun 2016, komposisi sampah organik adalah yang terbesar kedua setelah sampah plastik dan sangat berpotensi mengalami penambahan setiap tahunnya. Tujuan dari penelitian ini adalah untuk membuat perancangan pembangkit listrik tenaga sampah organik zero waste di Kabupaten Tegal, dengan studi kasus di Tempat Pembuangan Akhir (TPA sampah Penujah. Objek dalam penelitian ini adalah sistem pengolahan sampah organik yang ada di Kabupaten Tegal dengan menggunakan sistem pengolahan sampah zero waste. Sistem pengolahan sampah organik zero waste adalah sistem pengolahan sampah yang tidak menghasilkan sampah kembali. Jadi, diharapkan jumlah sampah organik akan berkurang secara bertahap. Sampah organik dapat dirubah menjadi biogas melalui proses fermentasi yang dibantu oleh bakteri secara anaerob di dalam reaktor biodigester. Biogas tersebut ditampung di dalam tempat penampungan untuk kemudian didistribusikan ke dalam genset biogas sebagai bahan bakar pembangkit listrik. Sisa pengolahan biogas dapat dirubah menjadi pupuk cair dan pupuk kompos yang bernilai ekonomis.

Development and implementation of tPA clot lysis activity assay using ACL TOP™ hemeostasis testing system in QC laboratories

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Lichun Huang

2017-12-01

Full Text Available This report describes the design, development, validation and long-term performance of tPA clot lysis activity assay using Advanced Chemistry Line Total Operational Performance (ACL TOP™ Homeostasis Testing System. The results of the study demonstrated robust and stable performance of the analytical method. The accuracy of the assay, expressed by percent recovery is 98–99%. The intermediate precision and repeatability precision, expressed as Relative Standard Deviation (RSD, was 3% and less than 2% respectively. The validated range is from 70% to 130% of the target potency of 5.8 × 105 IU/mg. The linearity of this range, expressed in correlation coefficient, is 0.997. After the assay is transferred to a QC laboratory, the assay retained high accuracy and precision with a success rate of >99%. Keywords: Potency assay, Clot lysis, Comparability, Automation

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.

Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus

DEFF Research Database (Denmark)

Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

1994-01-01

The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated...... with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure......-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant...

Time-Dependent Density Functional Theory Analysis of Triphenylamine-Functionalized Graphene Doped with Transition Metals for Photocatalytic Hydrogen Production.

Science.gov (United States)

Mota, Elder A V; Neto, Abel F G; Marques, Francisco C; Mota, Gunar V S; Martins, Marcelo G; Costa, Fabio L P; Borges, Rosivaldo S; Neto, Antonio M J C

2018-07-01

The electronic structures and optical properties of triphenylamine-functionalized graphene (G-TPA) doped with transition metals, using water as a solvent, were theoretically investigated to verify the efficiency of photocatalytic hydrogen production with the use of transition metals. This study was performed by Density Functional Theory and Time-dependent Density Functional Theory through Gaussian 09W software, adopting the B3LYP functional for all structures. The 6-31g(d) basis set was used for H, C and N atoms, and the LANL2DZ basis set for transition metals using the Effective Core Potentials method. Two approaches were adopted: (1) using single metallic dopants (Ni, Pd, Fe, Os and Pt) and (2) using combinations of Ni with the other dopants (NiPd, NiPt, NiFe and NiOs). The DOS spectra reveal an increase of accessible states in the valence shell, in addition to a gap decrease for all dopants. This doping also increases the absorption in the visible region of solar radiation where sunlight is most intense (400 nm to 700 nm), with additional absorption peaks. The results lead us to propose the G-TPA structures doped with Ni, Pd, Pt, NiPt or NiPd to be novel catalysts for the conversion of solar energy for photocatalytic hydrogen production, since they improve the absorption of solar energy in the range of interest for solar radiation; and act as reaction centers, reducing the required overpotential for hydrogen production from water.

Ultrafast two-photon absorption optical thresholding of spectrally coded pulses

Science.gov (United States)

Zheng, Z.; Shen, S.; Sardesai, H.; Chang, C.-C.; Marsh, J. H.; Karkhanehchi, M. M.; Weiner, A. M.

1999-08-01

We report studies on two-photon absorption (TPA) GaAs p-i-n waveguide photodetectors as optical thresholders for proposed ultrashort pulse optical code-division multiple-access (CDMA) systems. For either chirped optical pulses or spectrally phase coded pseudonoise bursts, the TPA photocurrent response reveals a strong pulseshape dependence and shows good agreement with theoretical predictions and results from conventional SHG measurements. The performance limits of the TPA optical thresholders set by the encoded bandwidth in the spectral encoding-decoding process are also discussed based on numerical simulations. Our results show the feasibility of applying such devices as nonlinear intensity discriminators in ultrahigh-speed optical network applications.

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

International Nuclear Information System (INIS)

Wun, T.C.; Capuano, A.

1987-01-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above

Immunoradiometric quantitation of tissue plasminogen activator-related antigen in human plasma: crypticity phenomenon and relationship to plasma fibrinolysis

Energy Technology Data Exchange (ETDEWEB)

Wun, T.C.; Capuano, A.

1987-05-01

A two-site immunoradiometric assay for tissue plasminogen activator (tPA) antigen has been developed using immunoaffinity purified antibody. Various treatments enhanced the detection of tPA antigen in the plasma samples. Maximum detection was obtained by acidification of plasma to pH 4.8 to 6.5 or addition of 0.5 mol/L of L-lysine or L-arginine. Acidification or addition of lysine to plasma is also required for maximum immunoadsorption of plasma tPA antigen on anti-tPA-Ig-sepharose. These results indicate that plasma tPA antigen is partially cryptic to antibody in untreated plasma. The plasma tPA antigen isolated by immunoadsorption of either untreated plasma or acidified plasma on anti-tPA-Ig-sepharose consists mainly of a 100-kd plasminogen activator species as determined by fibrin-agar zymography. The 100-kd activity is possibly a tPA:inhibitor complex. A standardized sample preparation method was conveniently adopted by mixing 3 vol of plasma and 1 vol of 2 mol/L of L-lysine for the assay. Reconstitution and recovery studies showed that the method is specific and permits full detection of both free tPA and tPA:inhibitor complex. The validity of the assay is further supported by the finding that the spontaneous plasma fibrinolysis previously demonstrated to be dependent on plasma tPA antigen is correlated with tPA antigen content. Using the standardized assay, we found that tPA antigen concentrations in 16 blood bank plasmas are equivalent to 3.7 to 20 ng of 60 kd tPA/mL. In all the plasma tested, more than half of the antigen is undetected unless the plasma is treated as described above.

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...

Stability of the octameric structure affects plasminogen-binding capacity of streptococcal enolase.

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Amanda J Cork

Full Text Available Group A Streptococcus (GAS is a human pathogen that has the potential to cause invasive disease by binding and activating human plasmin(ogen. Streptococcal surface enolase (SEN is an octameric α-enolase that is localized at the GAS cell surface. In addition to its glycolytic role inside the cell, SEN functions as a receptor for plasmin(ogen on the bacterial surface, but the understanding of the molecular basis of plasmin(ogen binding is limited. In this study, we determined the crystal and solution structures of GAS SEN and characterized the increased plasminogen binding by two SEN mutants. The plasminogen binding ability of SENK312A and SENK362A is ~2- and ~3.4-fold greater than for the wild-type protein. A combination of thermal stability assays, native mass spectrometry and X-ray crystallography approaches shows that increased plasminogen binding ability correlates with decreased stability of the octamer. We propose that decreased stability of the octameric structure facilitates the access of plasmin(ogen to its binding sites, leading to more efficient plasmin(ogen binding and activation.

Multi-mode interference revealed by two photon absorption in silicon rich SiO2 waveguides

International Nuclear Information System (INIS)

Manna, S.; Ramiro-Manzano, F.; Mancinelli, M.; Turri, F.; Pavesi, L.; Ghulinyan, M.; Pucker, G.

2015-01-01

Photoluminescence (PL) from Si nanocrystals (NCs) excited by two-photon absorption (TPA) has been observed in Si nanocrystal-based waveguides fabricated by plasma enhanced chemical vapor deposition. The TPA excited photoluminescence emission resembles the one-photon excited photoluminescence arising from inter-band transitions in the quantum confined Si nanocrystals. By measuring the non-linear transmission of waveguides, a large TPA coefficient of β up to 10 −8  cm/W has been measured at 1550 nm. These values of β depend on the Si NCs size and are two orders of magnitude larger than the bulk silicon value. Here, we propose to use the TPA excited visible PL emission as a tool to map the spatial intensity profile of the 1550 nm propagating optical modes in multimode waveguides. In this way, multimode interference has been revealed experimentally and confirmed through a finite element simulation

Cloning of the staurosporine biosynthetic gene cluster from Streptomyces sp. TP-A0274 and its heterologous expression in Streptomyces lividans.

Science.gov (United States)

Onaka, Hiroyasu; Taniguchi, Shin-ichi; Igarashi, Yasuhiro; Furumai, Tamotsu

2002-12-01

Staurosporine is a representative member of indolocarbazole antibiotics. The entire staurosporine biosynthetic and regulatory gene cluster spanning 20-kb was cloned from Streptomyces sp. TP-A0274 and sequenced. The gene cluster consists of 14 ORFs and the amino acid sequence homology search revealed that it contains three genes, staO, staD, and staP, coding for the enzymes involved in the indolocarbazole aglycone biosynthesis, two genes, staG and staN, for the bond formation between the aglycone and deoxysugar, eight genes, staA, staB, staE, staJ, staI, staK, staMA, and staMB, for the deoxysugar biosynthesis and one gene, staR is a transcriptional regulator. Heterologous gene expression of a 38-kb fragment containing a complete set of the biosynthetic genes for staurosporine cloned into pTOYAMAcos confirmed its role in staurosporine biosynthesis. Moreover, the distribution of the gene for chromopyrrolic acid synthase, the key enzyme for the biosynthesis of indolocarbazole aglycone, in actinomycetes was investigated, and rebD homologs were shown to exist only in the strains producing indolocarbazole antibiotics.

Development of magnetic nanoparticle based calorimetric assay for the detection of bovine mastitis in cow milk.

Science.gov (United States)

Chinnappan, Raja; Al Attas, Sana; Kaman, Wendy E; Bikker, Floris J; Zourob, Mohammed

2017-04-15

Mastitis in dairy cattle is an inflammatory reaction of the udder tissue. Mastitis increases plasmin levels, leading to an increased proteolysis of milk proteins such as casein, resulting in a significant decrease in milk quality and related dairy products. Due to its key-role in mastitis, we used plasmin proteolytic activity as a biomarker for the detection of mastitis in bovine mastitic milk. Inspired by earlier studies on protease activity using mastitic milk samples, we developed a simple colorimetric assay to distinguish mastitic milk from milk derived from healthy animals. The plasmin substrate coupled to magnetic nanoparticles form a black self-assembled monolayer on a gold sensor surface. In the presence of increased levels of plasmin, the substrate is cleaved and the peptide fragment attached to the magnetic beads, will be attracted by the magnet which is present under the sensor strips revealing the golden surface. We found the area of the golden color surface proportional to plasmin activity. The sensitivity of this method was determined to be 1 ng/ml of plasmin in vitro. Next, we tested the biosensor using mastitis positive milk of which infection is confirmed by bacterial cultures. This newly developed colorimetric biosensor has high potential in applications for the diagnosis of mastitis with potential spin offs to health, food and environmental sectors. Copyright © 2017 Elsevier Inc. All rights reserved.

Fitoremediasi Tanaman Akar Wangi (Vetiver zizanioides Terhadap Tanah Tercemar Logam Kadmium (Cd Pada Lahan TPA Tamangapa Antang Makassar

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Alfia Patandungan

2016-07-01

Full Text Available One example of soil contamination on land landfill is (TPA Makassar. The method of prevention is phytoremediation of the contaminated land. This study examined the ability of the plant will vetiver (Vetiver zizanioides in reducing the levels of Cd in the soil. To increase the potential of these plants to remediate Cd, the soil where the plants grow is combined with compost in which bacteria within the compost might improve the absorption of Cd. Planting medium used is pure soil and compost from Tamangapa Makassar. Research carried out for 28 days with a variation of the study. The composition of the media that the contaminated soil (TT metal kadmium  (Cd  and compost (K with a ratio of 100% (TT: 0 K, 5 (TT: 1 (K, 4.5 (TT: 1.5 (K and 4 (TT: 2 (K. The results shwed that vetiver plants were able to absorb Cd of 0,298 mg/Kg so it can be concluded that the composition of the planting medium with a combination of compost less significant because the combination of the contaminated soil with compost are less precise in  helping vetiver plants accumulate or reduce metal pollution cadmium in  contaminated soil Tamangapa Antang Makassar.

Two-Photon Absorption Properties of Gold Fluorescent Protein: A Combined Molecular Dynamics and Quantum Chemistry Study.

Science.gov (United States)

Simsek, Yusuf; Brown, Alex

2018-05-09

Molecular dynamic (MD) simulations were carried out to obtain the conformational changes of the chromophore in the gold fluorescent protein (PDB ID: 1OXF). To obtain two-photon absorption (TPA) cross-sections, time dependent density functional theory (TD-DFT) computations were performed for chromophore geometries sampled along the trajectory. The TD-DFT computations used the CAM-B3LYP functional and 6-31+G(d) basis set with the conductor-like polarizable continuum model (PCM) with parameters for water. Results showed that two dihedral angles change remarkably over the simulation time. TPA cross-sections were found to average 20 GM for the excitation to S1 between 430 and 460 nm; however, the maximal and minimal values were 35GM and 5GM, respectively. Besides the effects of the dihedrals on the spectroscopic properties, some bond lengths affected the excitation energies and the TPA cross-sections significantly (up to ±25-30%) while the effects of bond angles were smaller (±5%). Overall the present results provide insight in the effects of conformational exibility on TPA (with gold fluorescent protein as a specific example) and suggest that further experimental measurements of TPA for gold fluorescent protein should be undertaken.

Ectopic overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells.

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Do Youn Jun

Full Text Available Human lysosomal-associated protein multispanning membrane 5 (LAPTM5 was identified by an ordered differential display-polymerase chain reaction (ODD-PCR as an up-regulated cDNA fragment during 12-O-tetradecanoylphorbol 13-acetate (TPA-induced differentiation of U937 cells into monocytes/macrophages. After TPA-treatment, the levels of LAPTM5 mRNA and protein increased and reached a maximum at 18-36 h. In healthy human tissues, LAPTM5 mRNA was expressed at high levels in hematopoietic cells and tissues, at low levels in the lung and fetal liver, and was not detected in other non-hematopoietic tissues. LAPTM5 mRNA was detected in immature malignant cells of myeloid lineage, such as K562, HL-60, U937, and THP-1 cells, and in unstimulated peripheral T cells, but was absent or barely detectable in lymphoid malignant or non-hematopoietic malignant cells. The LAPTM5 level in HL-60 cells increased more significantly during TPA-induced monocyte/macrophage differentiation than during DMSO-induced granulocyte differentiation. Ectopic expression of GFP-LAPTM5 or LAPTM5 in HeLa cells exhibited the localization of LAPTM5 to the lysosome. In HeLa cells overexpressing LAPTM5, the Mcl-1 and Bid levels declined markedly and apoptosis was induced via Bak activation, Δψm loss, activation of caspase-9, -8 and -3, and PARP degradation without accompanying necrosis. However, these LAPTM5-induced apoptotic events except for the decline of Bid level were completely abrogated by concomitant overexpression of Mcl-1. The pan-caspase inhibitor (z-VAD-fmk could suppress the LAPTM5-induced apoptotic sub-G1 peak by ~40% but failed to block the induced Δψm loss, whereas the broad-range inhibitor of cathepsins (Cathepsin Inhibitor I could suppress the LAPTM5-induced apoptotic sub-G1 peak and Δψm loss, by ~22% and ~23%, respectively, suggesting that the LAPTM5-mediated Δψm loss was exerted at least in part in a cathepsin-dependent manner. Together, these results

Ectopic overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells

Science.gov (United States)

Jun, Do Youn; Kim, Hyejin; Jang, Won Young; Lee, Ji Young; Fukui, Kiyoshi; Kim, Young Ho

2017-01-01

Human lysosomal-associated protein multispanning membrane 5 (LAPTM5) was identified by an ordered differential display-polymerase chain reaction (ODD-PCR) as an up-regulated cDNA fragment during 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced differentiation of U937 cells into monocytes/macrophages. After TPA-treatment, the levels of LAPTM5 mRNA and protein increased and reached a maximum at 18–36 h. In healthy human tissues, LAPTM5 mRNA was expressed at high levels in hematopoietic cells and tissues, at low levels in the lung and fetal liver, and was not detected in other non-hematopoietic tissues. LAPTM5 mRNA was detected in immature malignant cells of myeloid lineage, such as K562, HL-60, U937, and THP-1 cells, and in unstimulated peripheral T cells, but was absent or barely detectable in lymphoid malignant or non-hematopoietic malignant cells. The LAPTM5 level in HL-60 cells increased more significantly during TPA-induced monocyte/macrophage differentiation than during DMSO-induced granulocyte differentiation. Ectopic expression of GFP-LAPTM5 or LAPTM5 in HeLa cells exhibited the localization of LAPTM5 to the lysosome. In HeLa cells overexpressing LAPTM5, the Mcl-1 and Bid levels declined markedly and apoptosis was induced via Bak activation, Δψm loss, activation of caspase-9, -8 and -3, and PARP degradation without accompanying necrosis. However, these LAPTM5-induced apoptotic events except for the decline of Bid level were completely abrogated by concomitant overexpression of Mcl-1. The pan-caspase inhibitor (z-VAD-fmk) could suppress the LAPTM5-induced apoptotic sub-G1 peak by ~40% but failed to block the induced Δψm loss, whereas the broad-range inhibitor of cathepsins (Cathepsin Inhibitor I) could suppress the LAPTM5-induced apoptotic sub-G1 peak and Δψm loss, by ~22% and ~23%, respectively, suggesting that the LAPTM5-mediated Δψm loss was exerted at least in part in a cathepsin-dependent manner. Together, these results demonstrate that

Biomimetic Oxidation Studies. 11. Alkane Functionalization in Aqueous Solution Utilizing in Situ Formed [Fe(2)O(eta(1)-H(2)O)(eta(1)-OAc)(TPA)(2)](3+), as an MMO Model Precatalyst, Embedded in Surface-Derivatized Silica and Contained in Micelles.

Science.gov (United States)

Neimann, Karine; Neumann, Ronny; Rabion, Alain; Buchanan, Robert M.; Fish, Richard H.

1999-07-26

The biomimetic, methane monooxygenase enzyme (MMO) precatalyst, [Fe(2)O(eta(1)-H(2)O)(eta(1)-OAc)(TPA)(2)](3+) (TPA = tris[(2-pyridyl)methyl]amine), 1, formed in situ at pH 4.2 from [Fe(2)O(&mgr;-OAc)(TPA)(2)](3+), 2, was embedded in an amorphous silicate surface modified by a combination of hydrophilic poly(ethylene oxide) and hydrophobic poly(propylene oxide). The resulting catalytic assembly was found to be a biomimetic model for the MMO active site within a hydrophobic macroenvironment, allowing alkane functionalization with tert-butyl hydroperoxide (TBHP)/O(2) in an aqueous reaction medium (pH 4.2). For example, cyclohexane was oxidized to a mixture of cyclohexanone, cyclohexanol, and cyclohexyl-tert-butyl peroxide, in a ratio of approximately 3:1:2. The balance between poly(ethylene oxide) and poly(propylene oxide), tethered on the silica surface, was crucial for maximizing the catalytic activity. The silica-based catalytic assembly showed reactivity somewhat higher in comparison to an aqueous micelle system utilizing the surfactant, cetyltrimethylammonium hydrogen sulfate at its critical micelle concentration, in which functionalization of cyclohexane with TBHP/O(2) in the presence of 1 was also studied at pH 4.2 and was found to provide similar products: cyclohexanol, cyclohexanone, and cyclohexyl-tert-butyl peroxide, in a ratio of approximately 2:3:1. Moreover, the mechanism for both the silica-based catalytic assembly and the aqueous micelle system was found to occur via the Haber-Weiss process, in which redox chemistry between 1 and TBHP provides both the t-BuO(*)() and t-BuOO(*)()( )()radicals. The t-BuO(*)()( )()radical initiates the C-H functionalization reaction to form the carbon radical, followed by O(2) trapping, to provide cyclohexyl hydroperoxide, which produces the cyclohexanol and cyclohexanone in the presence of 1, whereas the coupling product emanates from t-BuOO(*)() and cyclohexyl radicals. A discussion concerning both approaches for

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Hee; Lee, Chang Ki [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Oral Cancer Research Institute, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Hwang, Young Sun [Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Park, Kwang-Kyun [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Chung, Won-Yoon [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of)], E-mail: wychung@yuhs.ac

2008-07-03

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H{sub 2}O{sub 2} formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-{kappa}B) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-{kappa}B activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-{kappa}B signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent.

Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

International Nuclear Information System (INIS)

Park, Jae Hee; Lee, Chang Ki; Hwang, Young Sun; Park, Kwang-Kyun; Chung, Won-Yoon

2008-01-01

Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H 2 O 2 formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-κB activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-κB signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent

Selection and characterization of camelid nanobodies towards urokinase-type plasminogen activator

DEFF Research Database (Denmark)

Kaczmarek, Jakub; Skottrup, Peter Durand

2015-01-01

Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease that plays a vital role in extracellular conversion of inactive plasminogen into catalytically active plasmin. Activated plasmin facilitates the release of several proteolytic enzymes, which control processes like perice...

Angiostatin generating capacity and anti-tumour effects of D-penicillamine and plasminogen activators.

NARCIS (Netherlands)

Groot-Besseling, R. de; Ruers, T.J.M.; Lamers-Elemans, I.L.; Maass, C.N.; Waal, R.M.W. de; Westphal, J.R.

2006-01-01

BACKGROUND: Upregulation of endogenous angiostatin levels may constitute a novel anti-angiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs). Next, plasmin excises

Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic Activity of Cell-Derived Microparticles.

Science.gov (United States)

Briens, Aurélien; Gauberti, Maxime; Parcq, Jérôme; Montaner, Joan; Vivien, Denis; Martinez de Lizarrondo, Sara

2016-01-01

Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu. They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells. Although detection and characterization of cell-derived MPs may be of high diagnostic and prognostic values in a number of human diseases, reliable measurement of their size, number and biological activity still remains challenging using currently available methods. In the present study, we developed a protocol to directly image and functionally characterize MPs using high-resolution laser-scanning confocal microscopy. Once trapped on annexin-V coated micro-wells, we developed several assays using fluorescent reporters to measure their size, detect membrane antigens and evaluate proteolytic activity (nano-zymography). In particular, we demonstrated the applicability and specificity of this method to detect antigens and proteolytic activities of tissue-type plasminogen activator (tPA), urokinase and plasmin at the surface of engineered MPs from transfected cell-lines. Furthermore, we were able to identify a subset of tPA-bearing fibrinolytic MPs using plasma samples from a cohort of ischemic stroke patients who received thrombolytic therapy and in an experimental model of thrombin-induced ischemic stroke in mice. Overall, this method is promising for functional characterization of cell-derived MPs.

Grinding as a method of meat texture evaluation.

Science.gov (United States)

Kenmegne Kamdem, A T; Hardy, J

1995-01-01

An electric grinder equipped with a torque/speed sensor was used to evaluate maximum grinding torque (T(max)) and total energy (TE) necessary to grind 150 g of uncooked meat. Texture profile analysis (TPA), relaxation and cutting tests were carried out and sample compositions were also determined. The degree of dependence between grinding, TPA, relaxation, cutting parameters and sample composition was checked. Results showed that grinding parameters (T(max) and TE) correlated better with TPA, relaxation and cutting parameters than with composition. In particular correlation coefficient of -0·92, -0·92 and 0·97 were obtained, respectively, between T(max) and relaxation percentage (%R), T(max) and destructuring coefficient at 25% conmpression (De(25)) and between T(max) and maximum cutting force (F(c)).

Two-photon spectroscopy study of edge absorption peculiarities in oxygen-octahedric ferroelectrics

International Nuclear Information System (INIS)

Shablaev, S.I.; Danishevskij, A.M.; Subashiev, V.K.

1984-01-01

Two-photon absorption (TPA) spectra of ferroelectric crystals with BaTiO 3 , KTaO 3 and SrTiO 3 perovskite strUcture Were obtained. The detailed investigation of temperature dependence of edge spectrum regions was conducted and on the basis of their analysis the indirect character of edge absorption was concluded for all mentioned crystals. TPA spectra of BaTiO 3 and KTaO 3 are characterized by the regions corresponding to one indirect edge TPA spectra of SrTiO 3 - to two indirect edges. The corresponding inter-zone gaps were determined for all investigated crystals, the energy of phonons, participating in indirect two photon transitions, inter-zone gaps, corresponding to direct transitions were determined as well

Urine albumin is a superior predictor of preeclampsia compared to urine plasminogen in type I diabetes patients

DEFF Research Database (Denmark)

Nielsen, Lise Hald; Jensen, Boye L; Fuglsang, Jens

2018-01-01

Pregnant women with type I diabetes mellitus (T1DM) are at increased risk of developing preeclampsia (PE). Plasminogen is aberrantly filtrated from plasma into tubular fluid in PE patients and activated to plasmin. Plasmin activates the epithelial sodium channel in the collecting ducts potentially...

Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

Directory of Open Access Journals (Sweden)

Ruey-Hwang Chou

Full Text Available Fisetin (3,3',4',7-tetrahydroxyflavone, a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.

Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

Science.gov (United States)

Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

2013-01-01

Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion. PMID:23940799

Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA

International Nuclear Information System (INIS)

Friedmann, P.S.; Wren, F.E.; Matthews, J.N.

1990-01-01

Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C

Studies of protonic self-diffusion and conductivity in 12-tungstophophoric acid hydrates by pulsed field gradient 1H NMR and ac Conductivity

International Nuclear Information System (INIS)

Slade, R.C.; Pressman, H.A.; Barker, J.; Strange, J.H.

1988-01-01

Temperature dependent protonic conductivities σ and 1/H self-diffusion coefficients, D, are reported for polycrystalline hydrates of 12-tungstophosphoric acid (TPA). Conductivities were measured using ac admittane spectrometry and diffusion coefficients by the pulsed field gradient NMR technique. Conductivities for the hydrates TPA.nH 2 O (n=6, 14, 21) increase with n. Examination of σ and D values and of activation techniques shows self-diffusion and conduction to occur by different mechanisms in the higher hydrates. 25 refs.; 14 figs.; 1 table

On the origin of exciton formation in dye doped Alq{sub 3} OLEDs

Energy Technology Data Exchange (ETDEWEB)

Gomez, J.A. [FFCLRP-USP, Departamento de Fisica, Sao Paulo (Brazil); Castro, F.A. [National Physical Laboratory, Materials Division, Teddington (United Kingdom); Nueesch, F. [Empa, Swiss Federal Laboratories for Materials Testing and Research, Laboratory for Functional Polymers, Duebendorf (Switzerland); Zuppiroli, L. [Institut des Materiaux, EPFL, Laboratoire d' Optoelectronique des Materiaux Moleculaire, Lausanne (Switzerland); Graeff, C.F.O. [FC-UNESP, Departamento de Fisica, Sao Paulo (Brazil)

2012-09-15

Electrically Detected Magnetic Resonance (EDMR) was used to investigate the influence of dye doping on spin-dependent exciton formation in aluminum (III) 8-hydroxyquinoline (Alq{sub 3}) based Organic Light Emitting Diodes (OLEDs) with different device structures. 4-(dicyanomethylene)-2-methyl-6-{l_brace}2-[(4-diphenylamino)-phenyl]ethyl{r_brace}-4H-pyran (DCM-TPA) and 5,6,11,12-tetraphenylnaphthacene (Rubrene) were used as dopants. Results at room temperature show significant differences on the EDMR spectra (g-factor and linewidth) of doped and undoped devices. Signals from DCM-TPA and Rubrene dye doped OLEDs showed strong temperature dependence, with signal intensity increasing by 2 orders of magnitude below 200 K for DCM-TPA dye doped OLEDs and increasing by {proportional_to}1 order of magnitude below 225 K for the Rubrene dye doped device, while undoped devices shows almost no temperature dependence. By adding a ''spacer'' layer of undoped Alq{sub 3} at the recombination zone, changes in bias voltage were used to shift the recombination from doped to undoped region and correlate that with changes in the EDMR spectrum. Our results are indicating that charge trapping on the dopant followed by recombination is the main mechanism of light emission in the investigated devices. (orig.)

Proteolytic activation of the epithelial sodium channel ENaC in preeclampsia examined with urinary exosomes

DEFF Research Database (Denmark)

Nielsen, Maria Ravn; Rytz, Mie; Frederiksen-Møller, Britta

2015-01-01

OBJECTIVES: Increased activity of the epithelial sodium channel (ENaC) in the kidneys may explain the coupling between proteinuria, edema, suppressed aldosterone and hypertension in preeclampsia. Preeclamptic women excrete plasminogen-plasmin in urine. In vitro, plasmin increases the activity...... as a positive control for the presence of collecting duct membrane. RESULTS: Urine plasmin-plasminogen/creatinine ratio was increased in the preeclampsia group (p... pregnancy and preeclampsia CONCLUSIONS: It is possible to examine collecting duct transport proteins in urine exosome from pregnant women including γ-ENaC, 2) Urine exosome fraction displays a variable pattern of γ-ENaC signal with a predominance of cleaved forms in both normal and preeclamptic women...

Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

Science.gov (United States)

Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

2011-06-01

Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

GnRH signalling pathways and GnRH-induced homologous desensitization in a gonadotrope cell line (alphaT3-1).

Science.gov (United States)

Poulin, B; Rich, N; Mas, J L; Kordon, C; Enjalbert, A; Drouva, S V

1998-07-25

Exposure of the gonadotrope cells to gonadotropin-releasing hormone (GnRH) reduces their responsiveness to a new GnRH stimulation (homologous desensitization). The time frame as well as the mechanisms underlying this phenomenon are yet unclear. We studied in a gonadotrope cell line (alphaT3-1) the effects of short as well as long term GnRH pretreatments on the GnRH-induced phospholipases-C (PLC), -A2 (PLA2) and -D (PLD) activities, by measuring the production of IP3, total inositol phosphates (IPs), arachidonic acid (AA) and phosphatidylethanol (PEt) respectively. We demonstrated that although rapid desensitization of GnRH-induced IP3 formation did not occur in these cells, persistent stimulation of cells with GnRH or its analogue resulted in a time-dependent attenuation of GnRH-elicited IPs formation. GnRH-induced IPs desensitization was potentiated after direct activation of PKC by the phorbol ester TPA, suggesting the involvement of distinct mechanisms in the uncoupling exerted by either GnRH or TPA on GnRH-stimulated PI hydrolysis. The levels of individual phosphoinositides remained unchanged under any desensitization condition applied. Interestingly, while the GnRH-induced PLA2 activity was rapidly desensitized (2.5 min) after GnRH pretreatments, the neuropeptide-evoked PLD activation was affected at later times, indicating an important time-dependent contribution of these enzymatic activities in the sequential events underlying the GnRH-induced homologous desensitization processes in the gonadotropes. Under GnRH desensitization conditions, TPA was still able to induce PLD activation and to further potentiate the GnRH-evoked PLD activity. AlphaT3-1 cells possess several PKC isoforms which, except PKCzeta, were differentially down-regulated by TPA (PKCalpha, betaII, delta, epsilon, eta) or GnRH (PKCbetaII, delta, epsilon, eta). In spite of the presence of PKC inhibitors or down-regulation of PKC isoforms by TPA, the desensitizing effect of the neuropeptide on

Bone assessment via thermal photoacoustic measurements

Science.gov (United States)

Feng, Ting; Kozloff, Kenneth M.; Hsiao, Yi-Sing; Tian, Chao; Perosky, Joseph; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

The feasibility of an innovative biomedical diagnostic technique, thermal photoacoustic (TPA) measurement, for nonionizing and non-invasive assessment of bone health is investigated. Unlike conventional photoacoustic PA methods which are mostly focused on the measurement of absolute signal intensity, TPA targets the change in PA signal intensity as a function of the sample temperature, i.e. the temperature dependent Grueneisen parameter which is closely relevant to the chemical and molecular properties in the sample. Based on the differentiation measurement, the results from TPA technique is less susceptible to the variations associated with sample and system, and could be quantified with improved accurately. Due to the fact that the PA signal intensity from organic components such as blood changes faster than that from non-organic mineral under the same modulation of temperature, TPA measurement is able to objectively evaluate bone mineral density (BMD) and its loss as a result of osteoporosis. In an experiment on well established rat models of bone loss and preservation, PA measurements of rat tibia bones were conducted over a temperature range from 370 C to 440 C. The slope of PA signal intensity verses temperature was quantified for each specimen. The comparison among three groups of specimens with different BMD shows that bones with lower BMD have higher slopes, demonstrating the potential of the proposed TPA technique in future clinical management of osteoporosis.

Theoretical Insight into Organic Dyes Incorporating Triphenylamine-Based Donors and Binary π-Conjugated Bridges for Dye-Sensitized Solar Cells

Directory of Open Access Journals (Sweden)

Shuxian Wei

2014-01-01

Full Text Available The design of light-absorbent sensitizers with sustainable and environment-friendly material is one of the key issues for the future development of dye-sensitized solar cells (DSSCs. In this work, a series of organic sensitizers incorporating alkoxy-substituted triphenylamine (tpa donors and binary π-conjugated bridges were investigated using density functional theory (DFT and time-dependent DFT (TD-DFT. Molecular geometry, electronic structure, and optical absorption spectra are analyzed in the gas phase, chloroform, and dimethylformamide (DMF solutions. Our results show that properly choosing the heteroaromatic atoms and/or adding one more alkoxy-substituted tpa group can finely adjust the molecular orbital energy. The solvent effect renders the HOMO-LUMO gaps of the tpa-based sensitizers decrease in the sequence of DMF solution < chloroform solution < gas phase. The absorption spectra are assigned to the ligand-to-ligand charge transfer (LLCT characteristics via transitions mainly from tpa, 3,4-ethylenedioxythiophene (edot, and alkyl-substituted dithienosilole (dts groups to edot, dts, and cyanoacrylic acid groups. The binary π-conjugated bridges play different roles in balancing the electron transfer and recombination for the different tpa-based sensitizers. The protonation/deprotonation effect has great effect on the HOMO-LUMO gaps and thus has great influence on the bands at the long wavelength region, but little influence on the bands at the short wavelength region.

Reducing Door-to-Needle Times using Toyota’s Lean Manufacturing Principles and Value Stream Analysis

Science.gov (United States)

Ford, Andria L.; Williams, Jennifer A.; Spencer, Mary; McCammon, Craig; Khoury, Naim; Sampson, Tomoko; Panagos, Peter; Lee, Jin-Moo

2012-01-01

Background Earlier tPA treatment for acute ischemic stroke increases efficacy, prompting national efforts to reduce door-to-needle times (DNTs). We utilized lean process improvement methodology to develop a streamlined IV tPA protocol. Methods In early 2011, a multi-disciplinary team analyzed the steps required to treat acute ischemic stroke patients with IV tPA, utilizing value stream analysis (VSA). We directly compared the tPA-treated patients in the “pre-VSA” epoch to the “post-VSA” epoch with regard to baseline characteristics, protocol metrics, and clinical outcomes. Results The VSA revealed several tPA protocol inefficiencies: routing of patients to room, then to CT, then back to room; serial processing of work flow; and delays in waiting for lab results. On 3/1/2011, a new protocol incorporated changes to minimize delays: routing patients directly to head CT prior to patient room, utilizing parallel process work-flow, and implementing point-of-care labs. In the pre-and post-VSA epochs, 132 and 87 patients were treated with IV tPA, respectively. Compared to pre-VSA, DNTs and percent of patients treated ≤60 minutes from hospital arrival were improved in the post-VSA epoch: 60 min vs. 39 min (pLean process improvement methodology can expedite time-dependent stroke care, without compromising safety. PMID:23138440

Reducing door-to-needle times using Toyota's lean manufacturing principles and value stream analysis.

Science.gov (United States)

Ford, Andria L; Williams, Jennifer A; Spencer, Mary; McCammon, Craig; Khoury, Naim; Sampson, Tomoko R; Panagos, Peter; Lee, Jin-Moo

2012-12-01

Earlier tissue-type plasminogen activator (tPA) treatment for acute ischemic stroke increases efficacy, prompting national efforts to reduce door-to-needle times. We used lean process improvement methodology to develop a streamlined intravenous tPA protocol. In early 2011, a multidisciplinary team analyzed the steps required to treat patients with acute ischemic stroke with intravenous tPA using value stream analysis (VSA). We directly compared the tPA-treated patients in the "pre-VSA" epoch with the "post-VSA" epoch with regard to baseline characteristics, protocol metrics, and clinical outcomes. The VSA revealed several tPA protocol inefficiencies: routing of patients to room, then to CT, then back to the room; serial processing of workflow; and delays in waiting for laboratory results. On March 1, 2011, a new protocol incorporated changes to minimize delays: routing patients directly to head CT before the patient room, using parallel process workflow, and implementing point-of-care laboratories. In the pre and post-VSA epochs, 132 and 87 patients were treated with intravenous tPA, respectively. Compared with pre-VSA, door-to-needle times and percent of patients treated ≤60 minutes from hospital arrival were improved in the post-VSA epoch: 60 minutes versus 39 minutes (PLean process improvement methodology can expedite time-dependent stroke care without compromising safety.

Size- and Wavelength-Dependent Two-Photon Absorption Cross-Section of CsPbBr3 Perovskite Quantum Dots

NARCIS (Netherlands)

Chen, Junsheng; Zidek, Karel; Chabera, Pavel; Liu, Dongzhou; Cheng, Pengfei; Nuuttila, Lauri; Al-Marri, Mohammed J.; Lehtivuori, Heli; Messing, Maria E.; Han, Keli; Zheng, Kaibo; Pullerits, Tonu

2017-01-01

All-inorganic colloidal perovskite quantum dots (QDs) based on cesium, lead, and halide have recently emerged as promising light emitting materials. CsPbBr3 QDs have also been demonstrated as stable two-photon-pumped lasing medium. However, the reported two photon absorption (TPA) cross sections for

Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells

Directory of Open Access Journals (Sweden)

Eun Ju Shin

2015-04-01

Full Text Available Poly-γ-glutamic acid (PGA is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose polymerase (PARP and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2 and inducible nitric oxide synthase (iNOS. Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study.

Photoreactivity of tiaprofenic acid and suprofen using pig skin as an ex vivo model.

Science.gov (United States)

Sarabia, Z; Hernández, D; Castell, J V; van Henegouwen, G M

2000-10-01

The skin is repeatedly exposed to solar ultraviolet radiation. Photoreaction of drugs in the body may result in phototoxic or photoallergic side effects. Non-steroidal anti-inflammatory drugs, such as tiaprofenic acid (TPA) and the closely related isomer suprofen (SUP) are frequently associated with photosensitive disorders; they may mediate photosensitised damage to lipids, proteins and nucleic acids. Using ex vivo pig skin as a model, we investigated the photodegradation of TPA and SUP, and photobinding of these drugs to protein by means of HPLC analysis and drug-directed antibodies. Both with keratinocytes, which were first isolated from the pig skin and thereafter exposed to UVA and with keratinocytes which were isolated from pig skin after the skin was UVA exposed, time-dependent photodegradation of TPA and SUP was found, beside photoadduct formation to protein. The results of this work show that: (a) TPA and SUP were photodecomposed with similar efficiency; major photoproducts detected were decarboxytiaprofenic acid (DTPA) and decarboxysuprofen (DSUP), respectively. (b) Both drugs form photoadducts, as concluded from recognition by drug-specific antibodies. Pig skin appears to be a good model for studying the skin photosensitising potential of drugs.

Docosahexaenoic Acid Inhibits Tumor Promoter-Induced Urokinase-Type Plasminogen Activator Receptor by Suppressing PKCδ- and MAPKs-Mediated Pathways in ECV304 Human Endothelial Cells.

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Sen Lian

Full Text Available The overexpression of urokinase-type plasminogen activator receptor (uPAR is associated with inflammation and virtually all human cancers. Despite the fact that docosahexaenoic acid (DHA has been reported to possess anti-inflammatory and anti-tumor properties, the negative regulation of uPAR by DHA is still undefined. Here, we investigated the effect of DHA on 12-O-tetradecanoylphorbol-13-acetate (TPA-induced uPAR expression and the underlying molecular mechanisms in ECV304 human endothelial cells. DHA concentration-dependently inhibited TPA-induced uPAR. Specific inhibitors and mutagenesis studies showed that PKCδ, JNK1/2, Erk1/2, NF-κB, and AP-1 were critical for TPA-induced uPAR expression. Application of DHA suppressed TPA-induced translocation of PKCδ, activation of the JNK1/2 and Erk1/2 signaling pathways, and subsequent AP-1 and NF-κB transactivation. In conclusion, these observations suggest a novel role for DHA in reducing uPAR expression and cell invasion by inhibition of PKCδ, JNK1/2, and Erk1/2, and the reduction of AP-1 and NF-κB activation in ECV304 human endothelial cells.

The Biochemistry and Regulation of S100A10: A Multifunctional Plasminogen Receptor Involved in Oncogenesis

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Patricia A. Madureira

2012-01-01

Full Text Available The plasminogen receptors mediate the production and localization to the cell surface of the broad spectrum proteinase, plasmin. S100A10 is a key regulator of cellular plasmin production and may account for as much as 50% of cellular plasmin generation. In parallel to plasminogen, the plasminogen-binding site on S100A10 is highly conserved from mammals to fish. S100A10 is constitutively expressed in many cells and is also induced by many diverse factors and physiological stimuli including dexamethasone, epidermal growth factor, transforming growth factor-α, interferon-γ, nerve growth factor, keratinocyte growth factor, retinoic acid, and thrombin. Therefore, S100A10 is utilized by cells to regulate plasmin proteolytic activity in response to a wide diversity of physiological stimuli. The expression of the oncogenes, PML-RARα and KRas, also stimulates the levels of S100A10, suggesting a role for S100A10 in pathophysiological processes such as in the oncogenic-mediated increases in plasmin production. The S100A10-null mouse model system has established the critical role that S100A10 plays as a regulator of fibrinolysis and oncogenesis. S100A10 plays two major roles in oncogenesis, first as a regulator of cancer cell invasion and metastasis and secondly as a regulator of the recruitment of tumor-associated cells, such as macrophages, to the tumor site.

Quinoa Starch Characteristics and Their Correlations with the Texture Profile Analysis (TPA) of Cooked Quinoa.

Science.gov (United States)

Wu, Geyang; Morris, Craig F; Murphy, Kevin M

2017-10-01

Starch characteristics significantly influence the functionality and end-use quality of cereals and pseudo-cereals. This study examined the composition and properties of starch from 11 pure varieties and 2 commercial samples of quinoa in relationship to the texture of cooked quinoa. Nearly all starch properties and characteristics differed among these samples. Results showed that total starch content of seeds ranged from 53.2 to 75.1 g/100 g apparent amylose content ranged from 2.7% to 16.9%; total amylose ranged from 4.7% to 17.3%; and the degree of amylose-lipid complex ranged from 3.4% to 43.3%. Amylose leaching ranged from 31 mg/100 g starch in "Japanese Strain" to 862 mg/100 g starch in "49ALC." "Japanese Strain" starch also exhibited the highest water solubility (4.5%) and the lowest swelling power (17). α-Amylase activity in "1ESP," "Col.#6197," "Japanese Strain," "QQ63," "Yellow Commercial," and "Red Commercial" (0.03 to 0.09 CU) were significantly lower than the levels of the other quinoa samples (0.20 to 1.16 CU). Additionally, gel texture, thermal properties, and pasting properties of quinoa starches were investigated. Lastly, correlation analysis showed that the quinoa samples with higher amylose content tended to yield harder, stickier, more cohesive, more gummy, and more chewy texture after cooking. A higher degree of amylose-lipid complex and amylose leaching were associated with softer and less chewy cooked quinoa TPA texture. Higher starch enthalpy correlated with firmer, more adhesive, more cohesive, and chewier texture. In sum, starch plays a significant role in the texture of cooked quinoa. The research determined starch characteristics among a diverse set of pure quinoa varieties and commercial samples, and identified the relationships between starch properties and cooked quinoa texture. The results can help breeders and food manufacturers to understand better the relationships among quinoa starch characteristics, cooked quinoa texture, and

Isosteric Vapor Pressure – Temperature Data for Water Sorption in Hardened Cement Paste: Enthalpy, Entropy and Sorption Isotherms at Different Temperatures

DEFF Research Database (Denmark)

Radjy, Fariborz; Sellevold, Erik J.; Hansen, Kurt Kielsgaard

. The accuracies for pressure, enthalpy and entropy are found to be 0.5% or less. PART II: The TPA-system has been used to generate water vapor pressure – temperature data for room temperature – and steam cured hardened cement pastes as well as porous vycor glass. The moisture contents range from saturated to dry...... and the temperatures range from 2 to 95 °C, differing for the specimen types. The data has been analyzed to yield differential enthalpy and entropy of adsorption, as well as the dependence of the relative vapor pressure on temperature at various constant moisture contents. The implications for the coefficient......PART I: In order to generate isosteric (constant mass) vapor pressure – temperature data (P-T data) for adsorbed pore water in hydrated cement paste, the Thermo Piestic Analysis system (the TPA system) described herein was developed. The TPA system generates high precision equilibrium isosteric P...

Resistance of germfree athymic nude mice to two-stage skin carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Holland, J.M.; Perkins, E.H.

1979-01-01

Germfree athymic and normal littermate mice were compared with respect to their relative sensitivity to single skin application of dimethylbenzanthacine followed either by croton oil or TPA applied as a co-carcinogen. In separate experiments the acute response of both phenotypes to TPA was assessed by histologic examination of skin as well as the incorporttion of tritiated thymidine into acid insoluble material obtained from the isolated epidermis. Nude mice were observed to be less, equal, or more sensitive than normal littermate to topical skin carcinogenesis depending upon experimental variables. The tendency of solvent to spread rapidly on the skin of nude mice appeared to have the greatest influence on susceptibility to papilloma induction. Other factors of potential, although unproven importance, include differences in skin structure, possibly associated with accelerated activity of hair follicles as well as resistance to both the inflammatory and hyperplasiogenic effects of TPA.

Induction of rat hepatic zinc thionein by phorbol ester-mediated protein kinase C pathway

Energy Technology Data Exchange (ETDEWEB)

Garrett, S.H.; Funk, A.E.; Brady, F.O.

1986-05-01

Metallothionein (MT) exists in rat liver mainly as a zinc protein. The levels of this protein fluctuate in response to a variety of internal and external stimuli. Among these inducers of MT are metals, glucocorticoids, catecholamines, and polypeptide hormones. Metals and glucocorticoids are primary inducers of MT, while the others operate either via adenylate cyclase/cAMP/cAMP-dependent protein kinase, or via phospholipase C/inositol 1,4,5-triphosphate, diacylglycerol/Ca/sup 2 +/-dependent protein kinase, protein kinase C. The authors have examined the role of the protein kinase C pathway in the induction of MT by using a phorbol ester, 12-O-tetradecanoyl-phorbol 13-acetate (TPA), to activate it. In vivo TPA is a good inducer of Zn/sub 7/-MT with an ED/sub 0.5/ of 26.5 nmoles/kg b.w. Maximal levels reached were about 7..mu..g Zn in MT/g liver, an induction increase of 8 to 10-fold. An inactive compound, 4..beta..-phorbol, and the vehicle (DMSO) did not stimulate the synthesis of Zn/sub 7/-MT. This induction by TPA requires de novo protein synthesis, as demonstrated by a cycloheximide/(/sup 35/S)-cysteine experiment. TPA stimulated Zn incorporation by 8.6-fold and (/sup 35/S)-cysteine incorporation by 4.8-fold during an 11h induction. These increases were blocked 100% by treatment with cycloheximide at -1 and +5h. These experiments have been repeated in cultured hepatocytes, using (/sup 35/S)-cysteine incorporation, slab SDS-PAGE, and autoradiography to quantitate MT levels.

Modification of N-Methyl-N-Nitrosourea initiated bladder carcinogenesis in Wistar rats by terephthalic acid

International Nuclear Information System (INIS)

Cui Lunbiao; Shi Yuan; Dai Guidong; Pan Hongxin; Chen Jianfeng; Song Ling; Wang Shouling; Chang, Hebron C.; Sheng Hongbing; Wang Xinru

2006-01-01

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis

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

Deregulation of the actin cytoskeleton and macropinocytosis in response to phorbol ester by the mutant protein kinase C gamma that causes spinocerebellar ataxia type 14

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Kazuhiro eYamamoto

2014-04-01

Full Text Available Several missense mutations in the protein kinase Cγ (γPKC gene have been found to cause spinocerebellar ataxia type 14 (SCA14, an autosomal dominant neurodegenerative disease. γPKC is a neuron-specific member of the classical PKCs and is activated and translocated to subcellular regions as a result of various stimuli, including diacylglycerol synthesis, increased intracellular Ca2+ and phorbol esters. We investigated whether SCA14 mutations affect the γPKC-related functions by stimulating HeLa cells with TPA (12-O-tetradecanoylpholbol 13-acetate, a type of phorbol ester. Wild-type (WT γPKC-GFP was translocated to the plasma membrane within 10 min of TPA stimulation, followed by its perinuclear translocation and cell shrinkage, in a PKC kinase activity- and microtubule-dependent manner. On the other hand, although SCA14 mutant γPKC-GFP exhibited a similar translocation to the plasma membrane, the subsequent perinuclear translocation and cell shrinkage were significantly impaired in response to TPA. Translocated WT γPKC colocalized with F-actin and formed large vesicular structures in the perinuclear region. The uptake of FITC-dextran, a marker of macropinocytosis, was promoted by TPA stimulation in cells expressing WT γPKC, and FITC-dextran was surrounded by γPKC-positive vesicles. Moreover, TPA induced the phosphorylation of MARCKS, which is a membrane-substrate of PKC, resulting in the translocation of phosphorylated MARCKS to the perinuclear region, suggesting that TPA induces macropinocytosis via γPKC activation. However, TPA failed to activate macropinocytosis and trigger the translocation of phosphorylated MARCKS in cells expressing the SCA14 mutant γPKC. These findings suggest that γPKC is involved in the regulation of the actin cytoskeleton and macropinocytosis in HeLa cells, while SCA14 mutant γPKC fails to regulate these processes due to its reduced kinase activity at the plasma membrane. This property might be involved in

Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway

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Freeman Robert S

2011-02-01

Full Text Available Abstract Background Thrombolytic therapy with tissue plasminogen activator (tPA benefits patients with acute ischemic stroke. However, tPA increases the risk for intracerebral bleeding and enhances post-ischemic neuronal injury if administered 3-4 hours after stroke. Therefore, combination therapies with tPA and neuroprotective agents have been considered to increase tPA's therapeutic window and reduce toxicity. The anticoagulant factor protein S (PS protects neurons from hypoxic/ischemic injury. PS also inhibits N-methyl-D-aspartate (NMDA excitotoxicity by phosphorylating Bad and Mdm2 which blocks the downstream steps in the intrinsic apoptotic cascade. To test whether PS can protect neurons from tPA toxicity we studied its effects on tPA/NMDA combined injury which in contrast to NMDA alone kills neurons by activating the extrinsic apoptotic pathway. Neither Bad nor Mdm2 which are PS's targets and control the intrinsic apoptotic pathway can influence the extrinsic cascade. Thus, based on published data one cannot predict whether PS can protect neurons from tPA/NMDA injury by blocking the extrinsic pathway. Neurons express all three TAM (Tyro3, Axl, Mer receptors that can potentially interact with PS. Therefore, we studied whether PS can activate TAM receptors during a tPA/NMDA insult. Results We show that PS protects neurons from tPA/NMDA-induced apoptosis by suppressing Fas-ligand (FasL production and FasL-dependent caspase-8 activation within the extrinsic apoptotic pathway. By transducing neurons with adenoviral vectors expressing the kinase-deficient Akt mutant AktK179A and a triple FKHRL1 Akt phosphorylation site mutant (FKHRL1-TM, we show that Akt activation and Akt-mediated phosphorylation of FKHRL1, a member of the Forkhead family of transcription factors, are critical for FasL down-regulation and caspase-8 inhibition. Using cultured neurons from Tyro3, Axl and Mer mutants, we show that Tyro3, but not Axl and Mer, mediates

Surface-expressed enolases of Plasmodium and other pathogens

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Anil Kumar Ghosh

2011-08-01

Full Text Available Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential, especially for organisms devoid of the Krebs cycle that depend solely on glycolysis for energy. Interestingly, enolase appears to serve a separate function in some organisms, in that it is also exported to the cell surface via a poorly understood mechanism. In these organisms, surface enolase assists in the invasion of their host cells by binding plasminogen, an abundant plasma protease precursor. Binding is mediated by the interaction between a lysine motif of enolase with Kringle domains of plasminogen. The bound plasminogen is then cleaved by specific proteases to generate active plasmin. Plasmin is a potent serine protease that is thought to function in the degradation of the extracellular matrix surrounding the targeted host cell, thereby facilitating pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also expresses surface enolase, and that this feature may be essential for completion of its life cycle. The therapeutic potential of targeting surface enolases of pathogens is discussed.

Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR

DEFF Research Database (Denmark)

Plesner, T; Behrendt, N; Ploug, M

1997-01-01

patients with the rare blood disease paroxysmal nocturnal hemoglobinuria (PNH) that fail to express glycosyl-phosphatidylinositol-anchored proteins including uPAR, show a very significantly reduced transmigration over an endothelial barrier. Cell-associated plasminogen activation by PNH......Several important functions have been assigned to the receptor for urokinase-type plasminogen activator, uPAR. As implied by the name, uPAR was first identified as a high affinity cellular receptor for urokinase plasminogen activator (uPA). It mediates the binding of the zymogen, pro......-uPA, to the plasma membrane where trace amounts of plasmin will initiate a series of events referred to as "reciprocal zymogen activation" where plasmin converts pro-uPA to the active enzyme, uPA, which in turn converts plasma membrane-associated plasminogen to plasmin. This is an efficient machinery to generate...

Privacy-Preserving Outsourced Auditing Scheme for Dynamic Data Storage in Cloud

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Tengfei Tu

2017-01-01

Full Text Available As information technology develops, cloud storage has been widely accepted for keeping volumes of data. Remote data auditing scheme enables cloud user to confirm the integrity of her outsourced file via the auditing against cloud storage, without downloading the file from cloud. In view of the significant computational cost caused by the auditing process, outsourced auditing model is proposed to make user outsource the heavy auditing task to third party auditor (TPA. Although the first outsourced auditing scheme can protect against the malicious TPA, this scheme enables TPA to have read access right over user’s outsourced data, which is a potential risk for user data privacy. In this paper, we introduce the notion of User Focus for outsourced auditing, which emphasizes the idea that lets user dominate her own data. Based on User Focus, our proposed scheme not only can prevent user’s data from leaking to TPA without depending on data encryption but also can avoid the use of additional independent random source that is very difficult to meet in practice. We also describe how to make our scheme support dynamic updates. According to the security analysis and experimental evaluations, our proposed scheme is provably secure and significantly efficient.

Quantitative Surface Chirality Detection with Sum Frequency Generation Vibrational Spectroscopy: Twin Polarization Angle Approach

International Nuclear Information System (INIS)

Wei, Feng; Xu, Yanyan; Guo, Yuan; Liu, Shi-lin; Wang, Hongfei

2009-01-01

Here we report a novel twin polarization angle (TPA) approach in the quantitative chirality detection with the surface sum-frequency generation vibrational spectroscopy (SFG-VS). Generally, the achiral contribution dominates the surface SFG-VS signal, and the pure chiral signal is usually two or three orders of magnitude smaller. Therefore, it has been difficult to make quantitative detection and analysis of the chiral contributions to the surface SFG-VS signal. In the TPA method, by varying together the polarization angles of the incoming visible light and the sum frequency signal at fixed s or p polarization of the incoming infrared beam, the polarization dependent SFG signal can give not only direct signature of the chiral contribution in the total SFG-VS signal, but also the accurate measurement of the chiral and achiral components in the surface SFG signal. The general description of the TPA method is presented and the experiment test of the TPA approach is also presented for the SFG-VS from the S- and R-limonene chiral liquid surfaces. The most accurate degree of chiral excess values thus obtained for the 2878 cm -1 spectral peak of the S- and R-limonene liquid surfaces are (23.7±0.4)% and (25.4±1.3)%, respectively.

Regulation of atrial natriuretic peptide (ANP) secretion

International Nuclear Information System (INIS)

Ruskoaho, H.; Toth, M.; Lang, R.E.; Unger, Th.; Garten, D.

1986-01-01

To investigate the role of calcium, protein kinase C and adenylate cyclase in the ANP secretion, the secretory responses from isolated perfused rat hearts to a calcium channel activator, Bay k8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluomethylphenyl)-2-pyridine-5-carboxylate), the calcium ionophore (A23187), the phorbol ester (12-0-tetradecanoylphorbol-13-acetate, TPA), and to forskolin were studied. ANP in perfusate was measured by radioimmunoassay 10 min before and during the infusion (30 min) of various agents at 2 min intervals. A23187 (5.7 x 10 -7 ) induced a sharp increase, whereas TPA (0.15 - 1.6 x 10 -7 ) caused a slowly progressive increase in ANP secretion. 4a-phorbol-12,13-didecanoate, a non-active phorbol ester, had no effect on ANP secretion. Bay k8644 (4 x 10 -7 ) and forskolin (1 x 10 -6 ) alone caused small but sustained increase in ANP secretion. The combination of TPA with Bay k8644, forskolin or A23187 stimulated ANP secretion higher than the calculated additive value for each agent. Dibuturyl-cAMP (1.6 x 10 -4 ) pretreatment also enhanced TPA-induced ANP release. 8-Bromo-cGMP (1.3 x 10 -4 ) and sodium nitroprusside (9 x 10 -5 ) alone had no effect, but both attenuated the TPA-induced ANP secretion. The results suggest that atrial cardiocytes possess at least two different secretory pathways for ANP secretion, which are probably dependent on protein kinase C and cyclic AMP

Examination of the signal transduction pathways leading to upregulation of tissue type plasminogen activator by Porphyromonas endodontalis in human pulp cells.

Science.gov (United States)

Huang, F-M; Chen, Y-J; Chou, M-Y; Chang, Y-C

2005-12-01

To investigate the tissue type plasminogen activator (t-PA) activity in human pulp cells stimulated with Porphyromonas endodontalis (P. endodontalis) in the absence or presence of p38 inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002. The supernatants of P. endodontalis were used to evaluate t-PA activity in human pulp cells using casein zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search for possible signal transduction pathways, SB203580, U0126 and LY294002 were added to test how they modulated the t-PA activity. The main casein secreted by human pulp cells migrated at 70 kDa and represented t-PA. Secretion of t-PA was found to be stimulated with P. endodontalis during 2-day cultured period (P endodontalis stimulated t-PA production respectively (P endodontalis stimulated t-PA production (P > 0.05). Porphyromonas endodontalis enhances t-PA production in human pulp cells, and the signal transduction pathways p38 and MEK are involved in the inhibition of t-PA.

A Comparison of the 2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain

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Sarah Nickolls

2011-01-01

Full Text Available GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.

Long-term stability of recombinant tissue plasminogen activator at -80 C

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Sperling Matthew

2009-06-01

Full Text Available Abstract Background Recombinant tissue plasminogen activator (tPA is a thrombolytic widely used clinically in the treatment of acute thrombotic disease such as ischemic stroke, myocardial infarction, and deep venous thrombosis. This has led to much interest in tPA based lytic therapies leading to laboratory based in-vitro and in-vivo investigations using this drug. However, tPA reconstituted in solution exhibits full activity for only 6–8 hours, according to the manufacturer. Therefore, methods to store reconstituted tPA for long durations while maintaining activity would be of assistance to laboratories using this enzyme. Findings In this work, the enzymatic activity of tPA stored at -80 C over time was measured, using an ELISA technique that measured the amount of active tPA bound to plasminogen activator inhibitor 1 (PAI-1 in a given sample. Sample of tPA solution mixed to a concentration of 1 (mg/ml were stored in cryogenic vials at -80 C for up to 7 years. For a given sample, aliquots were assayed for tPA activity, and compared with a tPA standard to determine relative enzymatic activity. Results are reported as means with standard errors, and 12 measurements were performed for each sample age. Conclusion There was no decrease in tPA activity for samples stored up to 7 years. Such cryogenic storage is a viable method for the preservation of tPA solution for laboratory investigations of tPA-based lytic therapies.

Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration.

Science.gov (United States)

Guthoff, Rainer; Guthoff, Tanja; Meigen, Thomas; Goebel, Winfried

2011-01-01

To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration. Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months. The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas). From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

Polarization dependence of two-photon transition intensities in rare-earth doped crystals

Energy Technology Data Exchange (ETDEWEB)

Le Nguyen, An-Dien [Univ. of California, Berkeley, CA (United States)

1996-05-01

A polarization dependence technique has been developed as a tool to investigate phonon scattering (PS), electronic Raman scattering (ERS), and two-photon absorption (TPA) transition intensities in vanadate and phosphate crystals. A general theory for the polarization dependence (PD) of two-photon transition intensities has been given. Expressions for the polarization dependent behavior of two-photon transition intensities have been tabulated for the 32 crystallographic point groups. When the wavefunctions for the initial and final states of a rare-earth doped in crystals are known, explicit PD expressions with no unknown parameters can be obtained. A spectroscopic method for measuring and interpreting phonon and ERS intensities has been developed to study PrVO₄, NdVO₄, ErVO₄, and TmVO₄ crystals. Relative phonon intensities with the polarization of the incident and scattered light arbitrarily varied were accurately predicted and subsequently used for alignment and calibration in ERS measurements in these systems for the first time. Since ERS and PS intensities generally follow different polarization curves as a function of polar angles, the two can be uniquely identified by comparing their respective polarization behavior. The most crucial application of the technique in ERS spectroscopy is the establishment of a stringent test for the Axe theory. For the first time, the F₁/F₂ ratio extracted from the experimental fits of the ERS intensities were compared with those predicted by theories which include both the second- and third-order contributions. Relatively good agreement between the fitted values of F₁/F₂ and the predicted values using the second-order theory has been found.

Regulation of 2-5A Dependent RNase at the Level of its Phosphorylation

Science.gov (United States)

1991-06-26

extract as follows: 25 ul wheat germ extract 10 ul H2O 1 ul RNasin ribonuclease inhibitor (40 u/ml) 7 ul ImM amino acid mixture 1 ul IM...diacylglycerol (DAG) 2. TPA 3. Indolactam Figure 6. Chemical structure of: 1. H-7 (A kinase inhibitor) 2. okadaic acid (A phosphatase inhibitor) Figure 7...elevating agents: Forskolin and Cholera toxin Figure 17. Down-regulation of 2-5A-depRNase by Okadaic 77 acid : A phosphatase inhibitor Figure 18

Solution-processable red-emission organic materials containing triphenylamine and benzothiodiazole units: synthesis and applications in organic light-emitting diodes.

Science.gov (United States)

Yang, Yi; Zhou, Yi; He, Qingguo; He, Chang; Yang, Chunhe; Bai, Fenglian; Li, Yongfang

2009-06-04

Three solution-processable red-emissive organic materials with a hole-transporting unit triphenylamine (TPA) as the core part and a D-pi-A bipolar structure as the branch part, TPA-BT (single-branched molecule), b-TPA-BT (bibranched molecule), and t-TPA-BT (tribranched molecule), were synthesized by the Heck coupling reaction. Herein, for the D-pi-A push-pull structure, we use TPA as the electron donor, benzothiodiazole (BT) as the electron acceptor, and the vinylene bond as the pi-bridge connecting the TPA and BT units. The compounds exhibit good solubility in common organic solvents, benefited from the three-dimensional spatial configuration of TPA units and the branch structure of the molecules. TPA-BT, b-TPA-BT, and t-TPA-BT show excellent photoluminescent properties with maximum emission peaks at ca. 630 nm. High-performance red-emission organic light-emitting diodes (OLEDs) were fabricated with the active layer spin coated from a solution of these compounds. The OLED based on TPA-BT displayed a low turn-on voltage of 2.0 V, a maximum luminance of 12192 cd/m2, and a maximum current efficiency of 1.66 cd/A, which is among the highest values for the solution-processed red-emission OLEDs. In addition, high-performance white-light-emitting diodes (WLEDs) with maximum luminance around 4400 cd/m2 and maximum current efficiencies above 4.5 cd/A were realized by separately doping the three TPA-BT-containing molecules as red emitter and poly(6,6'-bi-(9,9'-dihexylfluorene)- co-(9,9'-dihexylfluorene-3-thiophene-5'-yl)) as green emitter into blue poly(9,9-dioctylfluorene-2,7-diyl) host material with suitable weight ratios.

Intravenous Tissue Plasminogen Activator Can Be Safely Given without Complete Blood Count Results Back.

Directory of Open Access Journals (Sweden)

Yi Dong

Full Text Available It is well known that the efficacy of intravenous (i.v. tissue plasminogen activator (tPA is time-dependent when used to treat patients with acute ischemic strokes.Our study examines the safety issue of giving IV tPA without complete blood count (CBC resulted.This is a retrospective observational study by examining the database from Huashan Hospital in China and OSF/INI Comprehensive Stroke Center in United States. Patient data collected included demographics, occurrence of symptomatic intracranial hemorrhage, door to needle intervals, National Institute of Health Stroke Scale scores on admission, CBC results on admission and follow-up modified Rankin Scale scores. Linear regression and multivariable logistic regression analysis were used to identify factors that would have an impact on door-to-needle intervals.Our study included 120 patients from Huashan Hospital and 123 patients from INI. Among them, 36 in Huashan Hospital and 51 in INI received i.v. tPA prior to their CBC resulted. Normal platelet count was found in 98.8% patients after tPA was given. One patient had thrombocytopenia but no hemorrhagic event. A significantly shorter door to needle interval (DTN was found in the group without CBC resulted. There was also a difference in treatment interval between the two hospitals. Door to needle intervals had a strong correlation to onset to treatment intervals and NIHSS scores on admission.In patients presented with acute ischemic stroke, the risk of developing hemorrhagic event is low if i.v. tPA is given before CBC has resulted. The door to needle intervals can be significantly reduced.

Limited evidence for third-party affiliation during development in wild chimpanzees (Pan troglodytes schweinfurthii).

Science.gov (United States)

Miller, Jordan A; Stanton, Margaret A; Lonsdorf, Elizabeth V; Wellens, Kaitlin R; Markham, A Catherine; Murray, Carson M

2017-09-01

Examining the ontogeny of conflict-mitigating behaviours in our closest living relatives is an important component of understanding the evolutionary origins of cooperation in our species. In this study, we used 26 years of data to investigate the emergence of third-party affiliation (TPA), defined as affiliative contact given to recipients of aggression by uninvolved bystanders (regardless of initiation), in wild immature eastern chimpanzees ( Pan troglodytes schweinfurthii ) of Gombe National Park, Tanzania. We also characterized TPA by mothers in the same dataset as an adult benchmark for interpreting immature TPA patterns. In summary, we found that immatures did not express TPA as measured by grooming between the ages of 1.5 and 12.0 years, and that there was limited evidence that immatures expressed TPA via play. We also found that mothers did express TPA to offspring, although mothers did not show TPA towards non-offspring. Cases of TPA by mothers to other adults were too few to analyse separately. These results contrast with findings from captive studies which found that chimpanzees as young as 6 years of age demonstrated TPA. We argue that within-species variation in the expression of TPA, both in immatures and adulthood, provides evidence that the conflict management behaviours of young chimpanzees may be heavily influenced by social, ecological and demographic factors.

Activation of Pro-uPA is Critical for Initial Escape from the Primary Tumor and Hematogenous Dissemination of Human Carcinoma Cells

DEFF Research Database (Denmark)

Bekes, Erin; Deryugina, Elena; Kuprianova, Tatyana

2011-01-01

disseminating variant of the human PC-3 prostate carcinoma cell line, PC-hi/diss, as a prototype of aggressive carcinomas to investigate the mechanisms whereby pro-uPA activation and uPA-generated plasmin functionally contribute to specific stages of metastasis. The PC-hi/diss cells secrete and activate...... significant amounts of pro-uPA, leading to efficient generation of plasmin in solution and at the cell surface. In a mouse orthotopic xenograft model, treatment with the specific pro-uPA activation-blocking antibody mAb-112 significantly inhibited local invasion and distant metastasis of the PC-hi/diss cells....... To mechanistically examine the uPA/plasmin-mediated aspects of tumor cell dissemination, the anti pro-uPA mAb-112 and the potent serine protease inhibitor, aprotinin, were utilized in parallel in a number of in vivo assays modeling various rate-limiting steps in early metastatic spread. Our findings demonstrate...

Quality control of techetium 99m radiopharmacentical in nuclear medicine

International Nuclear Information System (INIS)

Darte, L.

1981-03-01

Gel chromatography column scanning (GCS) is a new method for radiochemical quality control. GCS techniques for Technetium-99m radiopharmaceuticals in nuclear medicine have been developed for use in both research and routine clinical work. The dependence on several of the parameters of the GCS method have been investigated, e.g. type of gel, column dimensions, eluent, equilibration, elution volume, flow rate and resolution of the recording system (radiochromatographic scanner or scintillation camera). The GCS method has been compared with conventional gel filtration, thinlayer cromatography (TLC) and paper cromatography (PC). The GCS method is to be preferred due to few artifacts, much information, good reproducibility, rapidity, simplicity and the convenience of the test. The GCS method has been applied to the development of labelling techniques for the new radiopharmaceuticals Tc-99m plasmin and Tc-99m unithiol (2.3 dimercaptopropane sodiumsulphonate), use for investigating deep vein thrombosis and renal cortical morphology respectively. The GCS method has also been applied for studying some labelling parameters, the radiochemical purity and the labelling of Tc-99m macroaggregated albumin, Tc-99m pyrophosphate, Tc-99m methylenedisphosphate, in addition to Tc-99m plasmin and Tc-99m unithiol. (Author)

An RCT on treatment of palatally displaced canines with RME and/or a transpalatal arch.

Science.gov (United States)

Baccetti, Tiziano; Sigler, Lauren M; McNamara, James A

2011-12-01

To investigate the effect of rapid maxillary expansion (RME) and/or transpalatal arch (TPA) therapy in combination with deciduous canine extraction on the eruption of palatally displaced canines (PDCs). Hundred and twenty subjects were enrolled in an RCT based on PDCs diagnosed on panoramic radiographs and they were randomly assigned to one of four study groups. Three treatment groups (TGs) (RME followed by TPA therapy plus extraction of deciduous canines, RME/TPA/EC group, 40 subjects; TPA therapy plus extraction of deciduous canines, TPA/EC group, 25 subjects; extraction of deciduous canines, EC group, 25 subjects) were analyzed. A control group (CG, 30 subjects) received no orthodontic treatment. Prevalence rates of eruption of PDCs in the three TGs were compared with the CG at T2. Predictive features at T1 for successful canine eruption were tested in the three TGs. The prevalence of canine eruption was 80 per cent for the RME/TPA/EC group, 79 per cent for the TPA/EC group, 62.5 per cent for the EC group, versus 28 per cent in the CG, with statistically significant differences between all the groups, with the exception of the comparison between RME/TPA/EC and TPA/EC. Predictive pretreatment variables for the success of treatment were less severe sectors of canine displacement, prepubertal stages of skeletal maturity, and an open root apex of PDCs. The use of a TPA in absence of RME can be equally effective than the RME/TPA combination in PDC cases not requiring maxillary expansion, thus reducing the burden of treatment for the patient.

Two-Photon-Absorption Scheme for Optical Beam Tracking

Science.gov (United States)

Ortiz, Gerardo G.; Farr, William H.

2011-01-01

A new optical beam tracking approach for free-space optical communication links using two-photon absorption (TPA) in a high-bandgap detector material was demonstrated. This tracking scheme is part of the canonical architecture described in the preceding article. TPA is used to track a long-wavelength transmit laser while direct absorption on the same sensor simultaneously tracks a shorter-wavelength beacon. The TPA responsivity was measured for silicon using a PIN photodiode at a laser beacon wavelength of 1,550 nm. As expected, the responsivity shows a linear dependence with incident power level. The responsivity slope is 4.5 x 10(exp -7) A/W2. Also, optical beam spots from the 1,550-nm laser beacon were characterized on commercial charge coupled device (CCD) and complementary metal-oxide semiconductor (CMOS) imagers with as little as 13.7 microWatts of optical power (see figure). This new tracker technology offers an innovative solution to reduce system complexity, improve transmit/receive isolation, improve optical efficiency, improve signal-to-noise ratio (SNR), and reduce cost for free-space optical communications transceivers.

The synthesis of phosphatidylalcohols in HL-60 cells

International Nuclear Information System (INIS)

Tettenborn, C.S.

1988-01-01

This study focuses upon the phenomenon that 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulates a pathway for the synthesis of phosphatidylalcohols in HL-60 cells during the differentiation of these cells to macrophages. Using exogenous ethanol as a substrate for this pathway, the synthesis of phosphatidylethanol is induced by TPA well before full expression of differentiation. Experiments done in whole cell cultures demonstrated that this pathway could utilize a wide range of other alcohols as substrates, including glycerol, a potential endogenous substrate. Using radiolabeling and iodine-staining as criteria, this TPA-inducible pathway was shown to result in a dramatic alteration of phospholipid composition, depending on the availability of the alcohol headgroup. A cell-free system was developed to explore the enzymatic reactions involved in phosphatidylalcohol synthesis, a main goal of these studies. For this purpose, the lipid pools of HL-60 cells were prelabeled with [ 3 H]arachidonic acid in the absence of ethanol and total cell homogenates were prepared by sonication. The ability of the cell lysates to synthesize phosphatidylethanol was assayed after addition of ethanol to the system

Bolus dose response characteristics of single chain urokinase plasminogen activator and tissue plasminogen activator in a dog model of arterial thrombosis.

Science.gov (United States)

Badylak, S F; Voytik, S; Klabunde, R E; Henkin, J; Leski, M

1988-11-15

Tissue plasminogen activator (t-PA) and single chain urokinase-plasminogen activator (scu-PA) are relatively "fibrin-specific" thrombolytic drugs with short plasma half lives of 6-8 minutes. Most treatment regimens with these agents utilize a bolus injection followed by continuous drug infusion, usually combined with anticoagulant therapy. The purpose of this study was to establish the dose-response characteristics for scu-PA and t-PA, when given as a single intravenous bolus injection, in a dog model of arterial thrombosis. Eight groups of 6 dogs each were given one of the following doses of scu-PA (mg/kg): 0.20, 0.50, 1.00, 2.00; or t-PA: 0.05, 0.10, 0.20; or an equivalent amount of saline (control group). All doses were given as a single bolus injection 60 minutes after formation of a totally occlusive femoral artery thrombus. Thrombolysis was measured by monitoring the continuous decrement of 125I activity from a radiolabelled thrombus. Ninety minutes after drug injection, all scu-PA treated dogs showed greater thrombolysis (30%, 45%, 56%, and 67%, respectively) than the control group (15%, p less than 0.01). The 0.10 and 0.20 mg/kg t-PA treated dogs showed greater thrombolysis (35% and 49%, respectively) than the control group (15%, p less than 0.01). Both scu-PA and t-PA caused a partial and dose-dependent decrease in alpha 2-antiplasmin activity but scu-PA caused a greater depletion (72% vs. 18%, respectively, p less than 0.05) at 60 minutes after the highest dose of drug administration. Both drugs showed a longer than expected thrombolytic effect based upon the known half lives. Neither drug caused significant changes in the prothrombin time, activated partial thromboplastin time, thrombin time, hematocrit, platelet count, or fibrin degradation product concentration. Single bolus injections of scu-PA and t-PA produce safe and effective thrombolysis in this dog model of arterial thrombosis.

A novel mechanism of skin tumor promotion involving interferon-gamma (IFNγ)/signal transducer and activator of transcription-1 (Stat1) signaling.

Science.gov (United States)

Bozeman, Ronald; Abel, Erika L; Macias, Everardo; Cheng, Tianyi; Beltran, Linda; DiGiovanni, John

2015-08-01

The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate (TPA) and 3-methyl-1,8-dihydroxy-9-anthrone (chrysarobin or CHRY) led to rapid phosphorylation of Stat1 on both tyrosine (Y701) and serine (S727) residues in epidermis. CHRY treatment also led to upregulation of unphosphorylated Stat1 (uStat1) at later time points. CHRY treatment also led to upregulation of interferon regulatory factor 1 (IRF-1) mRNA and protein, which was dependent on Stat1. Further analyses demonstrated that topical treatment with CHRY but not TPA upregulated interferon-gamma (IFNγ) mRNA in the epidermis and that the induction of both IRF-1 and uStat1 was dependent on IFNγ signaling. Stat1 deficient (Stat1(-/-) ) mice were highly resistant to skin tumor promotion by CHRY. In contrast, the tumor response (in terms of both papillomas and squamous cell carcinomas) was similar in Stat1(-/-) mice and wild-type littermates with TPA as the promoter. Maximal induction of both cyclooxygenase-2 and inducible nitric oxide synthase in epidermis following treatment with CHRY was also dependent on the presence of functional Stat1. These studies define a novel mechanism associated with skin tumor promotion by the anthrone class of tumor promoters involving upregulation of IFNγ signaling in the epidermis and downstream signaling through activated (phosphorylated) Stat1, IRF-1 and uStat1. © 2014 Wiley Periodicals, Inc.

Inhibition of interferon production in human fibroblasts by a tumor promoting phorbol ester

International Nuclear Information System (INIS)

Frankfort, H.M.; Vilcek, J.

1982-01-01

The effect of 12-0-tetradecanoylphorbol-13-acetate (TPA) on the induction of interferon in cultures of human fibroblasts was examined. TPA was found to inhibit polyinosinate-polycytidylate [poly(I) X poly(C)]-induced interferon production when added either before or with the inducer. A 3-hour pretreatment of FS-4 cells with TPA produced the greatest ihibitory effect. Partially inhibitory treatments with TPA caused a delay in interferon production. On the other hand, interferon yields were slightly enhanced by TPA added at 1 1/2 or 3 hours postinduction. No gross metabolic perturbations (e.g., inhibition of cellular protein or RNA synthesis) were detected which would explain the phenomenon. The inhibition of interferon production was a stereospecific event: biologically inactive derivatives of TPA (4-0-methyl TPA, 4-α-phorbol-12, 13-didecanoate and phorbol-12, 13-diacetate) had no effect on interferon production. Cellular proteases or nucleases did not appear to be involved in this process. The binding of labeled poly(I) X poly(C) to FS-4 cells was unaltered in TPA-treated cultures. In superinduced cultures (i.e., after enhancement of interferon yields by actinomycin D and cycloheximide), interferon production was generally less inhibited by TPA than after simple induction. Newcastle disease virus (NDV)-induced interferon synthesis in GM-258 cells was also inhibited by the phorbol ester. Both α (leukocyte) and β (fibroblast) interferon production was inhibited to a similar degree in TPA-treated cells inoculated with 0.1 or 1 plaque forming unit (PFU) of NDV per cell. Increasing the multiplicity of infection with NDV to 10 PFU per cell overcame the inhibitory action of TPA. We conclude that the site of TPA action is either the triggering (generation of the hypothetical inducing signal) or transcription of the interferom mRNA. (Author)

A triphenylamine substituted quinacridone derivative for solution processed organic light emitting diodes

NARCIS (Netherlands)

Pilz da Cunha, M.; Do, T.T.; Yambem, S.D.; Pham, H.D.; Chang, S.; Manzhos, S.; Katoh, R.; Sonar, P.

2018-01-01

We report on a novel quinacridone derivative design, namely, 2,9-bis(4-(bis(4-methoxyphenyl)amino)phenyl)-5,12-bis(2-ethylhexyl)-5,12-dihydroquinolino[2,3-b]acridine-7,14-dione (TPA-QA-TPA) for possible use as a solution processable emissive layer in organic light emitting diodes (OLEDs). TPA-QA-TPA

Triphenylamine based benzimidazole and benzothiazole: Synthesis and applications in fluorescent chemosensors and laser dyes

Energy Technology Data Exchange (ETDEWEB)

Yang, Yang [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033 (China); University of Chinese Academy of Sciences, Beijing 100039 (China); Li, Bin, E-mail: libinteacher@163.com [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033 (China); Zhang, Liming; Guan, Yunlong [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033 (China)

2014-01-15

Triphenylamine based fluorescent dyes TPA-benzimidazole and TPA-benzothiazole have been designed and synthesized. The TPA-benzimidazole chemosensor was tested for a number of metal ions and found to exhibit binding affinity for Fe{sup 3+} and Hg{sup 2+} in acetonitrile, and the fluorescence quenching was achieved through a PET process. The appearance of an isosbestic point in absorption titrations and Job's plot analysis supported 1:1 stoichiometries for Fe{sup 3+} and Hg{sup 2+} ions. Laser experiments showed that under transversal pumping with a Q-switched Nd:YAG (355 nm) laser in toluene, TPA-benzothiazole exhibits efficient and stable amplified spontaneous emissions (ASE) at 436 nm. -- Highlights: • Triphenylamine based fluorescent dyes TPA-benzimidazole and TPA-benzothiazole have been designed and synthesized. • The TPA-benzimidazole exhibits binding affinity for Fe{sup 3+} and Hg{sup 2+} in acetonitrile and the fluorescence quenching was achieved through a PET process. • Under transversal pumping at 355 nm in toluene, TPA-benzothiazole exhibits efficient and stable amplified spontaneous emissions (ASE) in 436 nm.

Triphenylamine based benzimidazole and benzothiazole: Synthesis and applications in fluorescent chemosensors and laser dyes

International Nuclear Information System (INIS)

Yang, Yang; Li, Bin; Zhang, Liming; Guan, Yunlong

2014-01-01

Triphenylamine based fluorescent dyes TPA-benzimidazole and TPA-benzothiazole have been designed and synthesized. The TPA-benzimidazole chemosensor was tested for a number of metal ions and found to exhibit binding affinity for Fe 3+ and Hg 2+ in acetonitrile, and the fluorescence quenching was achieved through a PET process. The appearance of an isosbestic point in absorption titrations and Job's plot analysis supported 1:1 stoichiometries for Fe 3+ and Hg 2+ ions. Laser experiments showed that under transversal pumping with a Q-switched Nd:YAG (355 nm) laser in toluene, TPA-benzothiazole exhibits efficient and stable amplified spontaneous emissions (ASE) at 436 nm. -- Highlights: • Triphenylamine based fluorescent dyes TPA-benzimidazole and TPA-benzothiazole have been designed and synthesized. • The TPA-benzimidazole exhibits binding affinity for Fe 3+ and Hg 2+ in acetonitrile and the fluorescence quenching was achieved through a PET process. • Under transversal pumping at 355 nm in toluene, TPA-benzothiazole exhibits efficient and stable amplified spontaneous emissions (ASE) in 436 nm

Pembelajaran Kooperatif Tipe Make A Match Dalam Meningkatkan Penguasaan Kosa Kata Bahasa Arab Santri TPA Al-Barokah Hadimulyo Timur Metro Pusat

Directory of Open Access Journals (Sweden)

Muhammad Syaifullah

2016-12-01

Full Text Available Developments and changes in social life of nation and state ofIndonesia can not be separated effects of global change, the development ofscience and technology, arts and culture. Changes are constantly demandingthe need for improvement of the national education system, including thecompletion of the curriculum so as to create a society that is able to competeand adjust to the changing times. One of the goals of learning in schools(formal and non-formal is to improve learning outcomes and in learningthe Arabic language there are four skills that must be learned and masteredby students. The purpose of this research in general is improving resultsvocabulary mastery of Arabic students with a model of cooperative approachto make a match. This study uses classroom action research design. Subjectsin this study is the students of TPA elementary and junior high age children(7-12 years. The data in this study of information about the activities ofteachers and students and the results of beginning test and final test in eachcycle. The results of the application of learning vocabulary with the typecooperative learning methods make a match to mention that, there increasein learning outcomes associated with mastery Arabic vocabulary studentsthe significance of each cycle and also from the initial tests before action.The average class at beginning the pre-action test is 67 increased in the firstcycle 79 and increased again in the second cycle 91. From the test results itcan be seen improvements to the mastery Arabic vocabulary of students ineach cycle.

A literature-based cost analysis of tissue plasminogen activator for prevention of biliary stricture in donation after circulatory death liver transplantation.

Science.gov (United States)

Jones, J M; Bhutiani, N; Wei, D; Goldstein, L; Jones, C M; Cannon, R M

2018-04-17

This study sought to approximate the cost-effectiveness of tPA utilization for prevention of biliary strictures (PTBS) in donation after circulatory death liver transplantation (DCD-LT). Previously-reported PTBS rates in DCD-LT with and without tPA were used to calculate the number needed to treat (NNT) for prevention of one PTBS. The incremental cost of PTBS was then used to determine the cost effectiveness of tPA for prevention of PTBS. The incidence of PTBS in the setting of tPA administration was 20%, while incidence in patients without tPA use was 43% (p PTBS management, use of tPA in DCD-LT protocols was estimated to save $31,528 per PTBS prevented. Utilization of tPA in DCD-LT protocols represents one possible cost-effective strategy for prevention of PTBS in DCD-LT. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester

Energy Technology Data Exchange (ETDEWEB)

Horiguchi, J.; Spriggs, D.; Imamura, K.; Stone, R.; Luebbers, R.; Kufe, D.

1989-01-01

The treatment of human HL-60 promyelocytic leukemia cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcripts. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNS mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase, A/sub 2/ blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B/sub 4/. In contrast, the cyclooxygenase metabolite prostaglandin E/sub 2/ inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B/sub 4/ and prostaglandin E/sub 2/.

Iodinated Contrast Does Not Alter Clotting Dynamics in Acute Ischemic Stroke as Measured by Thromboelastography

Science.gov (United States)

McDonald, Mark M; Archeval-Lao, Joancy M; Cai, Chunyan; Peng, Hui; Sangha, Navdeep; Parker, Stephanie A; Wetzel, Jeremy; Riney, Stephen A; Cherches, Matt F; Guthrie, Greer J; Roper, Tiffany C; Kawano-Castillo, Jorge F; Pandurengan, Renga; Rahbar, Mohammad H; Grotta, James C

2014-01-01

Background and Purpose Iodinated contrast agents used for computed tomography angiography (CTA) may alter fibrin fiber characteristics and decrease fibrinolysis by tissue plasminogen activator (tPA). Thromboelastography (TEG™) measures the dynamics of coagulation and correlates with thrombolysis in acute ischemic stroke (AIS) patients. We hypothesized that receiving CTA prior to tPA will not impair thrombolysis as measured by TEG™. Methods AIS patients receiving 0.9 mg/kg tPA within 4.5 hours of symptom onset were prospectively enrolled. For CTA, 350 mg/dL of iohexol or 320 mg/dL of iodixanol at a dose of 2.2 ml/kg was administered. TEG™ was measured prior to tPA and 10-minutes after tPA bolus. CTA timing was left to the discretion of the treating physician. Results Of 136 AIS patients who received tPA, 47 had CTA prior to tPA bolus, and 42 had either CTA following tPA and post-tPA TEG™ draw or no CTA (non-contrast group). The median change in clot lysis (LY30) following tPA was 95.3% in the contrast group vs. 95.0% in the non-contrast group (p = 0.74). Thus, tPA-induced thrombolysis did not differ between contrast and non-contrast groups. Additionally, there was no effect of contrast on any pre-tPA TEG™ value. Conclusions Our data do not support an effect of iodinated contrast agents on clot formation or tPA activity. PMID:24370757

Triphenylamine - a 'new' stabilizer for nitrocellulose based propellants. Pt. 1: chemical stability studies

Energy Technology Data Exchange (ETDEWEB)

Wilker, Stephan; Heeb, Gerhard [WIWEB ASt Heimerzheim, Grosses Cent, 53913 Swisttal (Germany); Vogelsanger, Beat [Nitrochemie Wimmis AG, Niesenstr. 44, 3752 Wimmis (Switzerland); Petrzilek, Jan; Skladal, Jan [Explosia a.s. - Research Institute of Industrial Chemistry (VUPCH), 532 17 Pardubice (Czech Republic)

2007-04-15

Triphenylamine (TPA) was used for the first time in France in 1937 as a stabilizer for propellants. The stability of those samples was described as 'good'. Around 1950 an American group produced TPA stabilized propellants and investigated the decomposition mechanism. Apart from one single experiment in the 1970s no further attempts were made to take TPA as a stabilizer for propellants. With the background of an increasingly critical discussion about nitrosamines in propellants and their declaration of being carcinogenic, TPA revealed a renaissance since the year 2000. To achieve the goal of nitrosamine free propellants several TPA stabilized propellants were produced. Their processability, stability and ballistic properties were investigated. This publication summarizes the most important results of stability tests on more than 30 different TPA stabilized propellants including the decomposition mechanism, the synthesis of the consecutive products and their stabilizing properties. In addition, the internal compatibility of TPA with the most important propellant ingredients is discussed and its relative decomposition rate is compared with that of other stabilizers. In summary TPA is a suitable stabilizer for propellants. It has nevertheless two disadvantages. It is relatively rapidly consumed in double base formulations (which makes it difficult to pass the criteria of AOP-48, Ed. 2) and the stabilizing activity of the two major consecutive products 4-NO{sub 2}-TPA and especially 4,4{sup '}-di-NO{sub 2}-TPA is low. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

Structure of the Streptococcus pneumoniae Surface Protein and Adhesin PfbA

OpenAIRE

Suits, Michael D.; Boraston, Alisdair B.

2013-01-01

PfbA (plasmin- and fibronectin-binding protein A) is an extracellular Streptococcus pneumoniae cell-wall attached surface protein that binds to fibronectin, plasmin, and plasminogen. Here we present a structural analysis of the surface exposed domains of PfbA using a combined approach of X-ray crystallography and small-angle X-ray scattering (SAXS). The crystal structure of the PfbA core domain, here called PfbAβ, determined to 2.28 Å resolution revealed an elongated 12-stranded parallel β-he...

Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

Science.gov (United States)

Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

2017-07-01

Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, Padopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plasmonic Structure Enhanced Exciton Generation at the Interface between the Perovskite Absorber and Copper Nanoparticles

Science.gov (United States)

Lin, Kuen-Feng; Chiang, Chien-Hung; Wu, Chun-Guey

2014-01-01

The refractive index and extinction coefficient of a triiodide perovskite absorber (TPA) were obtained by fitting the transmittance spectra of TPA/PEDOT:PSS/ITO/glass using the transfer matrix method. Cu nanoplasmonic structures were designed to enhance the exciton generation in the TPA and to simultaneously reduce the film thickness of the TPA. Excitons were effectively generated at the interface between TPA and Cu nanoparticles, as observed through the 3D finite-difference time-domain method. The exciton distribution is advantageous for the exciton dissociation and carrier transport. PMID:25295290

Melanotransferrin induces human melanoma SK-Mel-28 cell invasion in vivo

International Nuclear Information System (INIS)

Bertrand, Yanick; Demeule, Michel; Michaud-Levesque, Jonathan; Beliveau, Richard

2007-01-01

The expression of melanotransferrin (MTf), a membrane-bound glycoprotein highly expressed in melanomas, is correlated with tumor vascularization and progression, suggesting a proinvasive function associated with MTf in malignant tumors. To test this hypothesis, we silenced MTf in human melanoma SK-MEL-28 cells using small interfering RNA (siRNA) and examined the plasmin activity and invasiveness of MTf-silenced melanoma. In vitro, the siRNA-mediated MTf knockdown inhibited by 58% the cell surface activation of plasminogen into plasmin. In addition, decreased expression of MTf in melanoma cells reduced cell migration. In vivo, we used a nude mice invasion model in which tissue factor (TF) induces vascular [ 125 I]-fibrin deposition following injection. Using this metastasis model, the invasive potential of MTf-silenced cells into the lungs was reduced by fivefold. Altogether, these findings strongly suggest that MTf overexpression in melanoma cells contributes to tumor progession by stimulating plasmin generation as well as cell migration and invasion

Electricity transmission. Transmission providers' duties to permit and possibilities to deny TPA to the network; Durchleitung von Strom. Pflichten und Verweigerungsmoeglichkeiten von Elektrizitaetsversorgungsunternehmen

Energy Technology Data Exchange (ETDEWEB)

Kasper, O.

2001-07-01

The author gives a full account of the new legal situation in the German electricity market and explains the recent changes induced by implementation of the legal framework of the European Union for building the internal electricity market, and by recent national legislation amending laws and regulations. The juridical changes and the new legal provisions and their effects in practice are explained in ten chapters. Some important keywords: the concept of third-party access (TPA) to electricity transmission networks - the IEM Directive of the EU - the reform of the German energy industry law - objectives and consequences of the reform - market deregulation - transmission pricing - competences of the national supervisory energy authority - national cartel law, market dominating position and abuse of a dominant market position - European cartel law. (orig./CB) [German] Der Autor gibt eine umfassende Darstellung der neuen Rechtslage im Strommarkt in Deutschland und erlaeutert die Veraenderungen, die sich aus den Vorgaben der Europaeischen Union zur Herstellung des Strom-Binnenmarkts und durch neue deutsche Gesetzgebung und Novellierung bestehender Regelungen ergaben. In zehn Kapiteln werden die neuen rechtlichen Bestimmungen und ihre Auswirkungen in der Praxis angesprochen. Einige wichtige Stichworte: Durchleitungsbegriff und Durchleitungsbedingungen - Binnenmarkt-Richtlinie Elektrizitaet - Neuregelung des deutschen Energiewirtschaftsrechts - Ziele und Folgen der Energierechtsreform - Deregulierung des Marktes - Bestimmung von Durchleitungsentgelten - Zustaendigkeit der nationalen Energieaufsichtsbehoerde - nationales Kartellrecht und kartellrechtlicher Missbrauchstatbestand - Europaeisches Kartellrecht. (orig./CB)

Antipain and 12-O-tetradecanoyl-phorbol-13-acetate

International Nuclear Information System (INIS)

Fujiwara, Y.; Tatsumi, M.

1980-01-01

Antipain (AP) and 12-O-tetradecanoyl-phorbooe-13-acetate (TPA) were tested in V79 Chinese hamster cells for cytotoxicity and effects on survival and 6-thioguanine-resistant (6TGsup(r)) mutation after UV-irradiation. AP and/or TPA were relatively non-cytotoxic and had no significant effects on UV survival. Despite their non-mutagenicity, the recovery of UV-induced 6TGsup(r) colonies was significantly enhanced by the pretreatment with either AP (0,5-2 mM) or TPA (0.1-1 μg/ml) only during the expression period before the 6TG selection at a low density of cells in the absence of AP or TPA. Such enhancing effects were maximal when AP or TPA was present during the late expression period after the mutation fixation and extensive dilution of DNA lesions. Reconstruction experiments revelaed the antgonisitc actions that TPA and AP tended to eliminate and increase, respectively, the metabolic co-operation. In the TPA-plus-AP treatment, AP abolished the TPA-enhanced recovery of induced mutants. Thus, it seems that TPA increases the mutant recovery langely through decreased metabolic co-operation and AP could modulate the mutation expression. Further, an error-prone inducible repair may not exist or, if it exists, AP may not inhibit it in V79 Chinese hamster cells. (orig.)

Binding of tissue plasminogen activator to human umbilical vein endothelial cells

International Nuclear Information System (INIS)

Beebe, D.P.

1987-01-01

The binding of purified, recombinant tissue plasminogen activator (tPA) to human umbilical vein endothelial cells (HUVEC) was studied in vitro using immunofluorescence as well as radiolabeled tPA. Immunofluorescence was performed on HUVEC grown on round glass coverslips using rabbit anti-human tPA and fluorescein-conjugated anti-rabbit immunoglobulin. Positive fluorescence was observed only after incubation of HUVEC with tPA. HUVEC were grown to confluence in 24-well tissue culture plates, washed, and incubated with a constant amount of 125 I-tPA and various concentrations of unlabeled tPA. The binding of tPA to HUVEC was found to be specific, saturable, and reversible. Scatchard analysis yielded as equilibrium constant (K/sub eq/) of 4.2 x 10 6 M -1 and 1.2 x 10 7 binding sites per cell. Binding was inhibited by positively charged amino acids and by D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone but not by carbohydrates including mannose, galactose, N-acetyl glucosamine and N-acetyl galactosamine. Neat human plasma abrogates but does not totally inhibit binding of tPA to HUVEC. Binding was neither enhanced nor inhibited by fibronectin. Although the affinity of binding of tPA to HUVEC is low, the endothelial cell may be involved in regulating plasma levels of tPA in vivo which may have therapeutic significance

Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase*S⃞

Science.gov (United States)

Kang, Nam Joo; Lee, Ki Won; Lee, Dong Eun; Rogozin, Evgeny A.; Bode, Ann M.; Lee, Hyong Joo; Dong, Zigang

2008-01-01

Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 μg/ml and 40 μm, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ mouse epidermal (JB6 P+) cells by 47 and 93%, respectively. The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-κB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 μm) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-κB, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation. PMID:18519570

A case-control study of the effectiveness of tissue plasminogen activator on 6 month patients--reported outcomes and health care utilization.

Science.gov (United States)

Lang, Catherine E; Bland, Marghuretta D; Cheng, Nuo; Corbetta, Maurizio; Lee, Jin-Moo

2014-01-01

We examined the benefit of tissue plasminogen activator (tPA), delivered as part of usual stroke management, on patient-reported outcomes and health care utilization. Using a case control design, patients who received tPA as part of usual stroke management were compared with patients who would have received tPA had they arrived to the hospital within the therapeutic time window. Data were collected from surveys 6 months after stroke using standardized patient-reported outcome measures and questions about health care utilization. Demographic and medical data were acquired from hospital records. Patients were matched on stroke severity, age, race, and gender. Matching was done with 1:2 ratio of tPA to controls. Results were compared between groups with 1-tailed tests because of a directionally specific hypothesis in favor of the tPA group. The tPA (n = 78) and control (n = 156) groups were matched across variables, except for stroke severity, which was better in the control group; subsequent analyses controlled for this mismatch. The tPA group reported better physical function, communication, cognitive ability, depressive symptomatology, and quality of life/participation compared with the control group. Fewer people in the tPA group reported skilled nursing facility stays, emergency department visits, and rehospitalizations after their stroke compared with controls. Reports of other postacute services were not different between groups. Although it is known that tPA reduces disability, this is the first study to demonstrate the effectiveness of tPA in improving meaningful, patient-reported outcomes. Thus, use of tPA provides a large benefit to the daily lives of people with ischemic stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Measurement of time processing ability and daily time management in children with disabilities.

Science.gov (United States)

Janeslätt, Gunnel; Granlund, Mats; Kottorp, Anders

2009-01-01

Improvement is needed in methods for planning and evaluating interventions designed to facilitate daily time management for children with intellectual disability, Asperger syndrome, or other developmental disorders. The aim of this study was to empirically investigate the hypothesized relation between children's time processing ability (TPA), daily time management, and self-rated autonomy. Such a relationship between daily time management and TPA may support the idea that TPA is important for daily time management and that children with difficulties in TPA might benefit from intervention aimed at improving daily time management. Participants were children aged 6 to 11 years with dysfunctions such as attention-deficit/hyperactivity disorder, autism, or physical or intellectual disabilities (N = 118). TPA was measured with the instrument KaTid. All data were transformed to interval measures using applications of Rasch models and then further analysed with correlation and regression analysis. The results demonstrate a moderate significant relation between the parents' ratings of daily time management and TPA of the children, and between the self-rating of autonomy and TPA. There was also a significant relation between self-ratings of autonomy and the parents' rating of the children's daily time management. Parents' ratings of their children's daily time management explain 25% of the variation in TPA, age of the children explains 22%, while the child's self-rating of autonomy can explain 9% of the variation in TPA. The three variables together explain 38% of the variation in TPA. The results indicate the viability of the instrument for assessing TPA also in children with disabilities and that the ability measured by KaTid is relevant for daily time management. TPA seems to be a factor for children's daily time management that needs to be taken into consideration when planning and evaluating interventions designed to facilitate everyday functioning for children with

Experimental and computational investigation of graphene/SAMs/n-Si Schottky diodes

Science.gov (United States)

Aydin, H.; Bacaksiz, C.; Yagmurcukardes, N.; Karakaya, C.; Mermer, O.; Can, M.; Senger, R. T.; Sahin, H.; Selamet, Y.

2018-01-01

We have investigated the effect of two different self-assembled monolayers (SAMs) on electrical characteristics of bilayer graphene (BLG)/n-Si Schottky diodes. Novel 4″bis(diphenylamino)-1, 1‧:3″-terphenyl-5‧ carboxylic acids (TPA) and 4,4-di-9H-carbazol-9-yl-1,1‧:3‧1‧-terphenyl-5‧ carboxylic acid (CAR) aromatic SAMs have been used to modify n-Si surfaces. Cyclic voltammetry (CV) and Kelvin probe force microscopy (KPFM) results have been evaluated to verify the modification of n-Si surface. The current-voltage (I-V) characteristics of bare and SAMs modified devices show rectification behaviour verifying a Schottky junction at the interface. The ideality factors (n) from ln(I)-V dependences were determined as 2.13, 1.96 and 2.07 for BLG/n-Si, BLG/TPA/n-Si and BLG/CAR/n-Si Schottky diodes, respectively. In addition, Schottky barrier height (SBH) and series resistance (Rs) of SAMs modified diodes were decreased compared to bare diode due to the formation of a compatible interface between graphene and Si as well as π-π interaction between aromatic SAMs and graphene. The CAR-based device exhibits better diode characteristic compared to the TPA-based device. Computational simulations show that the BLG/CAR system exhibits smaller energy-level-differences than the BLG/TPA, which supports the experimental findings of a lower Schottky barrier and series resistance in BLG/CAR diode.

Interleukin 1 induces early protein phosphorylation and requires only a short exposure for late induced secretion of β-endorphin in a mouse pituitary cell line

International Nuclear Information System (INIS)

Fagarasan, M.O.; Axelrod, J.; Bishop, J.F.; Rinaudo, M.S.

1990-01-01

Previous work has shown that prolonged pretreatment of a mouse anterior pituitary cell line, AtT-20 cells, with the cytokine interleukin 1 (IL-1) stimulates β-endorphin release and potentiates the secretion induced by many secretagogues. Desensitization of protein kinase C (PKC) by pretreatment with phorbol ester [phorbol 12-tetradecanoate 13-acetate (TPA)] for 8 hr abolished the secretion induced by TPA as well as the enhancement of TPA-induced β-endorphin release produced by IL-1. Desensitization of PKC only partly abolished the potentiating effects of IL-1 on corticotropin-releasing factor-induced β-endorphin secretion. In contrast, IL-1-induced β-endorphin release was independent of PKC. The authors observed that treatment of AtT-20 cells with IL-1 markedly phosphorylated 19-, 20-, and 60-kDa proteins within minutes, presumably by early activation of protein kinases. Prolonged treatment with TPA, which was shown to desensitize an 87-kDa protein (a substrate for PKC), had no effect on IL-1-induced phosphorylation of 20-, 60-, and 87-kDa proteins, indicating that the phosphorylation of these proteins does not involve PKC. IL-1 does not generate cAMP in AtT-20 cells, suggesting that a cAMP-dependent protein kinase is also not involved. These observations indicate that once IL-1 generates an early signal, its presence is no longer necessary for the subsequent secretion of β-endorphin

Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.

2009-11-01

We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

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)

Blood coagulation and fibrinolysis of the whole-body irradiated rabbits

International Nuclear Information System (INIS)

Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

1984-01-01

To study the effects of irradiation on blood coagulation and fibrinolysis, rabbits were irradiated with 60 Co γ-rays (whole-body: 0, 100, 400, 800, 1200 rads). Clotting time, activity of plasmin and plasminogen, and fibrinogen contents of irradiated rabbit plasma were measured at 4 days before, immediately after, and at 1, 3, 7, 10, and 14 days after irradiation. Both clotting times obtained by addition of (kaolin+phospholipid) which expressed effects on the total intrinsic coagulation system, and by addition of (Ca 2+ ) which expressed effects on the total extrinsic coagulation system, were prolonged with small dose irradiation (100 rads) immediately and 3 days after irradiation. However, with high dose irradiation (400-1200 rads), these clotting times were prolonged 1 day after irradiation. The times of manifestation of irradiation effects on clotting time were different in small and high dose irradiation. Plasmin activity was decreased immediately, 1 day after and recovered 3 days after irradiation. Plasminogen activity was markedly increased in 800 and 1200 rads irradiated groups from 3 days after irradiation. Conversion of plasminogen into plasmin was impaired by irradiation. Fibrinogen contents increased rapidly in all irradiated rabbits except for 100 rads from 1 day after irradiation. These results revealed decreased coagulation and fibrinolysis activities in rabbit blood, irradiation injury of both coagulation and fibrinolysis activation systems, and accumulation of the precursors of fibrin and plasmin (i.e., fibrinogen and plasminogen). (author)

Flat-on ambipolar triphenylamine/C60 nano-stacks formed from the self-organization of a pyramid-sphere-shaped amphiphile.

Science.gov (United States)

Liang, Wei-Wei; Huang, Chi-Feng; Wu, Kuan-Yi; Wu, San-Lien; Chang, Shu-Ting; Cheng, Yen-Ju; Wang, Chien-Lung

2016-04-21

A giant amphiphile, which is constructed with an amorphous nano-pyramid (triphenylamine, TPA) and a crystalline nano-sphere (C 60 ), was synthesized. Structural characterization indicates that this pyramid-sphere-shaped amphiphile ( TPA-C 60 ) forms a solvent-induced ordered phase, in which the two constituent units self-assemble into alternating stacks of two-dimensional (2D) TPA and C 60 nano-sheets. Due to the complexity of the molecular structure and the amorphous nature of the nano-pyramid, phase formation was driven by intermolecular C 60 -C 60 interactions and the ordered phase could not be reformed from the TPA-C 60 melt. Oriented crystal arrays of TPA-C 60 , which contain flat-on TPA/C 60 nano-stacks, can be obtained via a PDMS-assisted crystallization (PAC) technique. The flat-on dual-channel supramolecular structure of TPA-C 60 delivered ambipolar and balanced charge-transport characteristics with an average μ e of 2.11 × 10 -4 cm 2 V -1 s -1 and μ h of 3.37 × 10 -4 cm 2 V -1 s -1 . The anisotropic charge-transport ability of the pyramid-sphere-shaped amphiphile was further understood based on the lattice structure and the lattice orientation of TPA-C 60 revealed from electron diffraction analyses.

Biocatalyst including porous enzyme cluster composite immobilized by two-step crosslinking and its utilization as enzymatic biofuel cell

Science.gov (United States)

Chung, Yongjin; Christwardana, Marcelinus; Tannia, Daniel Chris; Kim, Ki Jae; Kwon, Yongchai

2017-08-01

An enzyme cluster composite (TPA/GOx) formed from glucose oxidase (GOx) and terephthalaldehyde (TPA) that is coated onto polyethyleneimine (PEI) and carbon nanotubes (CNTs) is suggested as a new catalyst ([(TPA/GOx)/PEI]/CNT). In this catalyst, TPA promotes inter-GOx links by crosslinking to form a large and porous structure, and the TPA/GOx composite is again crosslinked with PEI/CNT to increase the amount of immobilized GOx. Such a two-step crosslinking (i) increases electron transfer because of electron delocalization by π conjugation and (ii) reduces GOx denaturation because of the formation of strong chemical bonds while its porosity facilitates mass transfer. With these features, an enzymatic biofuel cell (EBC) employing the new catalyst is fabricated and induces an excellent maximum power density (1.62 ± 0.08 mW cm-2), while the catalytic activity of the [(TPA/GOx)/PEI]/CNT catalyst is outstanding. This is clear evidence that the two-step crosslinking and porous structure caused by adoption of the TPA/GOx composite affect the performance enhancement of EBC.

Effect of Lenient Steam Injection (LSI) heat treatment of bovine milk on the activities of some enzymes, the milk fat globule and pH

DEFF Research Database (Denmark)

Dickow, Jonatan A.; Nielsen, Martin Thorup; Hammershøj, Marianne

2012-01-01

This study investigated the effects of Lenient Steam Injection (LSI) treatment at temperatures 70–150 C on the enzymatic activities of the indigenous milk enzymes alkaline phosphatase, lactoperoxidase (LPO), xanthine oxidase (XO), lipoprotein lipase (LPL) and plasmin in comparison with two...... reference heat treatments of 63 C for 30 s and of 72 C for 15 s by indirect heating. Milk fat globule (MFG) size distributions and pH were also monitored. Alkaline phosphatase, LPO, XO and LPL activities decreased with increasing LSI temperature. Plasmin activity was increased at temperatures

Nonlinear Optical Properties of Aluminum Doped Zinc Oxide

Science.gov (United States)

Otieno, Calford O.

Nonlinear optical (NLO) materials are crucial to future progress in industrial and technological applications that involve intense light-matter interaction. While ZnO-related materials are known to possess good NLO properties, existing results on ZnO and AZO (Al-doped ZnO) are mostly available at a single wavelength or limited ranges. Therefore, NLO dispersions (wavelength dependences) are not entirely studied, especially at longer wavelengths far below the bandgap. It is important to explore wavelength dependences since doping can induce a drastic change in the NLO responses at varied spectral ranges via doping-induced subgap-state contributions. We present results of our studies on nonlinear harmonic generation from our samples, which include 1) second harmonic generation and 2) third harmonic generation precisely characterized by Maker fringes as a function of both Al doping and wavelength. We exhaustively discuss the possible cause for the modified optical nonlinearities observed in our AZO thin films and give detailed comparisons of our observations with the previous studies. We also present the results of open- and close-aperture Z-scans to characterize the two-photon absorption coefficient (TPA) and the nonlinear refractive index (NLR), respectively, of the AZO films. There was no clearcut evidence of monotonic dependence of TPA and NLR on doping. This presumably indicates that the overall effect is nontrivial and should be understood in terms of combined effects of bandgap shift and crystallinity upon varying the doping level. Most intriguingly, we found that NLR values from the closed-aperture Z-scan are very large by orders of magnitude when compared with the bulk counterparts. Similar observation was made for TPA values from the open-aperture Z-scan. To countercheck very large NLO absorption, we conducted simple intensity scan by varying the incident photon number on each sample but fixing the beam area to eliminate any possible errors related to optical

Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

OpenAIRE

Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

2013-01-01

Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient trave...

Low-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Cheng, Ji-Wei; Zhang, Xiao-Jing; Cheng, Li-Shan; Li, Guo-Yi; Zhang, Li-Jun; Ji, Kang-Xiang; Zhao, Qing; Bai, Yu

2018-02-01

Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial. We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes. Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08). Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

Science.gov (United States)

De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

2016-07-01

Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.

Synthesis and functional evaluation of a peptide derivative of 1-beta-D-arabinofuranosylcytosine.

Science.gov (United States)

Balajthy, Z; Aradi, J; Kiss, I T; Elödi, P

1992-09-04

We have synthesized a peptidyl prodrug derivative of 1-beta-D-arabinofuranosylcytosine (1) designed to be a selective substrate of plasmin. D-Val-Leu-Lys-ara-C (2) was obtained by coupling the protected peptide Cbz-D-Val-Leu-(N6-Cbz)Lys-OH and ara-C (1) by a water-soluble carbodiimide (EDCI), followed by the removal of the Cbz groups by using catalytic hydrogenolysis over Pd/C. The kinetic constant of hydrolysis of 2 in the presence of plasmin demonstrated effective release of 1. The amino group of 1, which is sensitive to the removal by cytidine deaminase, is protected in 2 by the formation of the amide bond resulting in a prolonged half-life of 2 in biological milieu. The antiproliferative efficiency of 2 against L1210 leukemic cells was significantly higher than that of 1. The activity of 2 was abolished in the presence of serine proteinase inhibitor, (4-amidinopheny)methanesulfonyl fluoride. These data indicate that 2 is a prodrug form of 1 in systems generating plasmin.

The effect of phorbols on metabolic cooperation between human fibroblasts

International Nuclear Information System (INIS)

Mosser, D.D.; Bols, N.C.

1982-01-01

Autoradiography has been used to study the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), 4-O-methyl TPA, and phorbol on metabolic cooperation between human diploid fibroblasts. When the donors, hypoxanthine-guanine phosphoribosyl transferase+ (HGPRT+) cells, and recipients, HGPRT- cells, were plated together in the presence of [ 3 H]hypoxanthine and either 4-O-methyl TPA or phorbol, nearly all interactions that developed in 4 h were positive for metabolic cooperation whereas when high concentrations of TPA were used, the number of positive interactions was significantly less than the control. If the phorbol analogs were added after the donors and recipients had made contact, the number of positive interactions was the same as the control in all cases. However, although primary recipients in the cultures that had been treated with phorbol had the same number of grains as those in the control, primary recipients in cultures that had been treated with TPA or high concentrations of 4-O-methyl TPA had significantly fewer grains than those in the control. TPA treatment for 4 h had no effect on total [ 3 H]hypoxanthine incorporation or incorporation into acid-soluble and acid-insoluble fractions. Thus, the effect of TPA on metabolic cooperation is interpreted as a reduction in the transfer of [ 3 H]nucleotides and is an indication of an interference with intercellular communication

Effects of 12-O-tetradecanoylphorbol-13-acetate in combination with gemcitabine on Panc-1 pancreatic cancer cells cultured in vitro or Panc-1 tumors grown in immunodeficient mice.

Science.gov (United States)

Zheng, Xi; Cui, Xiao-Xing; Gao, Zhi; Verano, Michael; Huang, Mou-Tuan; Liu, Yue; Rabson, Arnold B; Conney, Allan H

2012-12-01

In the present study, the effects of 12-O-tetra-decanoylphorbol-13-acetate (TPA) alone or in combination with gemcitabine on the growth of Panc-1 pancreatic cancer cells cultured in vitro or grown in NCr immunodeficient nude mice were investigated. Combinations of TPA and gemcitabine synergi-stically inhibited the growth and induced apoptosis in Panc-1 cells. The combination of TPA (0.16 nM) and gemcitabine (0.5 µM) induced a marked increase in phosphorylated c-Jun NH2-terminal kinase (JNK) in the Panc-1 cells. In animal experiments, NCr nude mice with established Panc-1 tumors received daily intraperitoneal (i.p.) injections of TPA (50 ng/g body weight/day) or gemcitabine (0.5 µg/g body weight/day) alone or in combination for 26 days. Treatment with daily i.p. injections of low doses of TPA or gemcitabine alone had a modest inhibitory effect on the growth of the tumors. However, the combination of low doses of TPA and gemcitabine more potently inhibited the growth of Panc-1 tumors than either agent used individually. Treatment with TPA or gemcitabine alone or in combination did not affect the body weight of the animals. Clinical trials with TPA alone or in combination with gemcitabine on patients with pancreatic cancer are warranted in order to confirm our results.

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Shu-Ling; Wu; Dong-Mei; Zhan; Shu-Hong; Xi; Xiang-Lian; He

2014-01-01

AIM:To investigate the role of tissue plasminogen activator(t-PA) and plasminogen activator inhibitor(PAI)in proliferative diabetic retinopathy(PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor(VEGF) expressions.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.

Anti-Inflammatory Effect of 3-O-[(6'-O-Palmitoyl-β-D-glucopyranosyl Sitosterol] from Agave angustifolia on Ear Edema in Mice

Directory of Open Access Journals (Sweden)

Elizabeth Hernández-Valle

2014-09-01

Full Text Available In Mexico Agave angustifolia has traditionally been used to treat inflammation. The aim of this study was to measure the anti-inflammatory effect of the extract of A. angustifolia, the isolation and identification of active compounds. From the acetone extract two active fractions were obtained, (AsF13 and AaF16. For the characterization of pharmacological activity, the acute inflammatory model of mouse ear edema induced with TPA was used. The tissue exposed to TPA and treatments were subjected to two analysis, cytokine quantification (IL-1β, IL-6, IL-10 and TNF-α and histopathological evaluation. The active fraction (AaF16 consisted principally of 3-O-[(6'-O-palmitoyl-β-D-glucopyranpsyl] sitosterol. In AaF13 fraction was identified β-sitosteryl glucoside (2 and stigmasterol (3. The three treatments tested showed a concentration-dependent anti-inflammatory effect (AaAc Emax = 33.10%, EC50 = 0.126 mg/ear; AaF13 Emax = 54.22%, EC50 = 0.0524 mg/ear; AaF16 Emax = 61.01%, EC50 = 0.050 mg/ear. The application of TPA caused a significant increase on level of IL-1β, IL-6 and TNFα compared with basal condition, which was countered by any of the experimental treatments. Moreover, the experimental treatments induced a significant increase in the levels of IL-4 and IL-10, compared to the level observed when stimulated with TPA. Therefore, the anti-inflammatory effect of Agave angustifolia, is associated with the presence of 3-O-[(6'-O-palmitoyl-β-D-glucopyranosyl] sitosterol.

Co-ordinate expression of activin A and its type I receptor mRNAs during phorbol ester-induced differentiation of human K562 erythroleukemia cells.

Science.gov (United States)

Hildén, K; Tuuri, T; Erämaa, M; Ritvos, O

1999-07-20

Activins were originally isolated based on their ability to stimulate follicle-stimulating hormone secretion but later they have been shown to regulate a number of different cellular functions such as nerve cell survival, mesoderm induction during early embryogenesis as well as hematopoiesis. We studied the regulation of activin A, a homodimer of betaA-subunits, mRNA and protein in K562 erythroleukemia cells, which are known to be induced toward the erythroid lineage in response to activin or TGF-beta or toward the megakaryocytic lineage by the phorbol ester protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). Here we show by Northern blot analysis as well as by Western and ligand blotting that TPA strongly promotes activin betaA-subunit mRNA and activin A protein expression in K562 cells in time- and concentration dependent manner. In contrast, neither activin A nor TGF-beta induced betaA-subunit mRNA expression during erythroid differentiation in K562 cells. Interestingly, whereas activin type II receptors are not regulated during K562 cell differentiation (Hilden et al. (1994) Blood 83, 2163-2170), we now show that the activin type I and IB receptor mRNAs are clearly induced by TPA but not by activin or TGF-beta. We also show that the inducing effect of TPA on expression of activin betaA-subunit mRNA is potentiated by the protein kinase A activator 8-bromo-cAMP. We conclude that activin A and its type I receptors appear to be co-ordinately up-regulated during megakaryocytic differentiation of K562 cells.

Modulation pf pulmonary surfactant secretion from alveolar type II cells by cytoplasmic free calcium ([Ca2+]/sub i/)

International Nuclear Information System (INIS)

Sano, K.; Voelker, D.R.; Mason, R.J.

1986-01-01

Ca 2+ is regulator of a variety of cellular functions including exocytosis. TPA and terbutaline have been shown to stimulate surfactant secretion from alveolar type II cells. The authors examined changes in [Ca 2+ ]/sub i/ and surfactant secretion by secretagogues in primary culture of alveolar type II cells. Cells were isolated from adult rats and were cultured for 24 h with 3 H-choline to label phosphatidylcholine. Percent secretion was determined by counting the lipids of cells and medium; cytotoxicity was excluded by measuring lactate dehydrogenase as cells and medium. [Ca 2+ ]/sub i/ was determined by measuring quin2 fluroescence of cells cultured on a glass coverslip. Ionomycin increased secretion as well as [Ca 2+ ] in dose dependent manner at the concentration from 25 to 400 nM. Ionomycin (50 nM) increased terbutaline-induced secretion in a synergistic manner but only increased TPA-induced secretion in an additive manner. Terbutaline mobilized [Ca 2+ ]/sub i/ from intracellular stores and increased [Ca 2+ ]/sub i/ by 20% from a basal level of 140 nM. TPA itself did not change [Ca 2+ ]/sub i/ but inhibited the effect of terbutaline on [Ca 2+ ]/sub i/. Loading of quin2 in the absence of extracellular calcium lowered [Ca 2+ ]/sub i/ from 143 nM to 31 nM. Lowering [Ca 2+ ]/sub i/ inhibited TPA- or terbutaline-induced secretion by 22% and 40% respectively. These results indicate that [Ca 2+ ]/sub i/ effects cAMp-induced secretion more than protein kinase C-mediated secretion in alveolar type II cells

Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study

DEFF Research Database (Denmark)

Gram, J; Bladbjerg, E-M; Møller, L

2000-01-01

OBJECTIVES: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects. DESIGN: Nested case-control study. Follow-up periods 7-15 years. SUBJECTS: Included in the study were 133 cases with coronary heart disease...... and 258 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum.......005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out...

Efficient optical trapping of CdTe quantum dots by femtosecond laser pulses

KAUST Repository

Chiang, Weiyi

2014-12-11

The development in optical trapping and manipulation has been showing rapid progress, most of it is in the small particle sizes in nanometer scales, substituting the conventional continuous-wave lasers with high-repetition-rate ultrashort laser pulse train and nonlinear optical effects. Here, we evaluate two-photon absorption in optical trapping of 2.7 nm-sized CdTe quantum dots (QDs) with high-repetition-rate femtosecond pulse train by probing laser intensity dependence of both Rayleigh scattering image and the two-photon-induced luminescence spectrum of the optically trapped QDs. The Rayleigh scattering imaging indicates that the two-photon absorption (TPA) process enhances trapping ability of the QDs. Similarly, a nonlinear increase of the two-photon-induced luminescence with the incident laser intensity fairly indicates the existence of the TPA process.

The internal market for natural gas: a political wager

International Nuclear Information System (INIS)

Claus, P.

1992-01-01

The European Commission's proposals for the introduction of third party access (TPA) to gas networks and the unbundling of production, transmission and distribution activities are examined. It is noted that the EC is dependent on imports from 3-4 countries outside the EC. It is argued that the introduction of TPA will result in a loss of security of supply, probable increase in prices to consumers, discrimination between classes of customers, a gradual transfer of commercial power from member states and the gas industry to suppliers outside the EC, and to the weakening of the market penetration of gas. The situation in the continental EC, and in the US and UK is compared, and the need for a stable confident climate for the gas industry is stressed. (UK)

Effects of two-photon absorption on all optical logic operation based on quantum-dot semiconductor optical amplifiers

Science.gov (United States)

Zhang, Xiang; Dutta, Niloy K.

2018-01-01

We investigate all-optical logic operation in quantum-dot semiconductor optical amplifier (QD-SOA) based Mach-Zehnder interferometer considering the effects of two-photon absorption (TPA). TPA occurs during the propagation of sub-picosecond pulses in QD-SOA, which leads to a change in carrier recovery dynamics in quantum-dots. We utilize a rate equation model to take into account carrier refill through TPA and nonlinear dynamics including carrier heating and spectral hole burning in the QD-SOA. The simulation results show the TPA-induced pumping in the QD-SOA can reduce the pattern effect and increase the output quality of the all-optical logic operation. With TPA, this scheme is suitable for high-speed Boolean logic operation at 320 Gb/s.

Ultrasound-targeted transfection of tissue-type plasminogen activator gene carried by albumin nanoparticles to dog myocardium to prevent thrombosis after heart mechanical valve replacement

Directory of Open Access Journals (Sweden)

Ji J

2012-06-01

Full Text Available Ji Jun, Ji Shang-Yi, Yang Jian-An, He Xia, Yang Xiao-Han, Ling Wen-Ping, Chen Xiao-LingDepartment of Pathology and Cardiovascular Surgery, Shenzhen Sun Yat-Sen Cardiovascular Hospital, Shenzhen, Guangdong, People's Republic of ChinaBackground: There are more than 300,000 prosthetic heart valve replacements each year worldwide. These patients are faced with a higher risk of thromboembolic events after heart valve surgery and long-term or even life-long anticoagulative and antiplatelet therapies are necessary. Some severe complications such as hemorrhaging or rebound thrombosis can occur when the therapy ceases. Tissue-type plasminogen activator (t-PA is a thrombolytic agent. One of the best strategies is gene therapy, which offers a local high expression of t-PA over a prolonged time period to avoid both systemic hemorrhaging and local rebound thrombosis. There are some issues with t-PA that need to be addressed: currently, there is no up-to-date report on how the t-PA gene targets the heart in vivo and the gene vector for t-PA needs to be determined.Aims: To fabricate an albumin nano-t-PA gene ultrasound-targeted agent and investigate its targeting effect on prevention of thrombosis after heart mechanic valve replacement under therapeutic ultrasound.Methods: A dog model of mechanical tricuspid valve replacement was constructed. A highly expressive t-PA gene plasmid was constructed and packaged by nanoparticles prepared with bovine serum albumin. This nanopackaged t-PA gene plasmid was further cross-linked to ultrasonic microbubbles prepared with sucrose and bovine serum albumin to form the ultrasonic-targeted agent for t-PA gene transfection. The agent was given intravenously followed by a therapeutic ultrasound treatment (1 MHz, 1.5 w/cm2, 10 minutes of the heart soon after valve replacement had been performed. The expression of t-PA in myocardium was detected with multiclonal antibodies to t-PA by the indirect immunohistochemical method

Comparative experimental studies into radioimmunoscintigraphy using radioactive antibodies in animals with HeLa cell carcinomas and Yoshida sarcomas

International Nuclear Information System (INIS)

Zettl, T.

1988-01-01

TPA-positive and TPA-negative tumour-bearing animal systems (HeLa cell carcinomas in RNU rats and Yoshida sarcomas in Wistar rats) were examined to show that the method of scanning can well be used to visualise tumour tissue. In this connection, further attempts were made to shed light on the specifity of immunoscintigraphy in the search for tumour tissue. 125-Iodine-anti-TPA was found to be a specific carcinoma-seeking substance. The amount of antibodies accumulating in the tumour was multiplied by previous intravenous treatment of test animals with unspecific immunoglobulin. In control studies using 125-iodine-immunoglobulin the site of the carcinomatous tissue could not be determined with sufficient diagnostic accuracy. It was found that the discriminating power of radioimmunoscintigraphy using 125-iodine-anti-TPA is quite unrelated to an increased circulation in the proliferating carcinomatous tissue. For the detection of TPA in HeLa cell carcinomas anti-TPA PAP stains were prepared. Radionuclide studies using 125-iodine-anti-TPA were also useful in the visualisation of the Yoshida sarcoma, even though this scores negative on TPA. Here, the amounts of radioactivity accumulating in the tumour were smaller than with the HeLa cell carcinoma. Moreover, peak levels were measured after no less than one day, as compared to the five days required for HeLa cell tumours to reach maximum levels. This finding would appear to provide presumptive evidence that there are other, unspecific mechanisms of tumour selectivity. (orig/MG) [de

Drivers of Costs Associated with Reperfusion Therapy in Acute Stroke: The IMS III Trial

Science.gov (United States)

Simpson, Kit N.; Simpson, Annie N.; Mauldin, Patrick D.; Hill, Michael D; Yeatts, Sharon D.; Spilker, Judith A.; Foster, Lydia D.; Khatri, Pooja; Martin, Renee; Jauch, Edward C.; Kleindorfer, Dawn; Palesch, Yuko Y.; Broderick, Joseph P.

2014-01-01

Background and Purpose The IMS III study tested the effect of IV t-PA alone as compared to IV t-PA followed by endovascular therapy and collected cost data to assess the economic implications of the two therapies. This report describes the factors affecting the costs of the initial hospitalization for acute stroke subjects from the US. Methods Prospective cost analysis of US subjects treated with IV t-PA alone or IV t-PA followed by endovascular therapy in the IMS III trial. Results compared to expected Medicare payments. Results The adjusted cost of a stroke admission in the study was $35,130 for subjects treated with endovascular therapy following IV t-PA treatment and $25,630 for subjects treated with IV t-PA alone (p<0.0001). Significant factors related to costs included treatment group, baseline NIH Stroke Scale, time from stroke onset to IV t-PA, age, stroke location, and comorbid diabetes. The mean cost for subjects who had routine use of general anesthesia as part of endovascular therapy was $46,444 as compared to $30,350 for those who did not have general anesthesia. The costs of embolectomy for IMS III subjects and patients from the NIS cohort exceeded the Medicare DRG payment in more than 75% of patients. Conclusion Minimizing the time to start of IV t-PA and decreasing the use of routine general anesthesia, may improve the cost-effectiveness of medical and endovascular therapy for acute stroke. PMID:24876261

Tetrapropylammonium ion inhibits Na, K-ATPase by blocking a K+-translocation step

International Nuclear Information System (INIS)

Forbush, B. III

1986-01-01

Tetrapropylammonium ion (TPA) has previously been shown to inhibit the Na/K pump in human red cells in competition with K + at extracellular sites. The author investigated the action of TPA on the release of 86 Rb from the occluded state of Na, K-ATPase from dog kidney. Like K + and Rb + , TPA is found to prevent the release of one (''s'' for slower) of two tightly bound 86 Rb ions when the enzyme is phosphorylated from P/sub i/; the data are consistent with TPA binding to the K + ''f'' (faster) site with an affinity of ∼5mM. When 86 Rb is bound to the ''s'' site and unlabelled Rb + or K + to the ''f'' site by an appropriate sequence of additions, the 86 Rb can be released by addition of ATP to bring about the E 2 -E]3! conformational change and translocation. In contrast when TPA is bound to the ''f'' site there is no release of 86 Rb from the ''s'' site when ATP is added, suggesting that the conformational change is prevented by the bulky TPA molecule at the transport site. Addition of Na + (without nucleotide or P/sub i/) brings about an extremely rapid (>100s -1 ) release of 86 Rb when TPA is bound. The reason for this is not yet clear, but the effect dramatically illustrates simultaneous occupancy of binding sites by K + , TPA, and Na +

Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Nam [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Dae Won [Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Kangneung 210-702 (Korea, Republic of); Jo, Hyo Sang; Shin, Min Jea; Ahn, Eun Hee; Ryu, Eun Ji; Yong, Ji In; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Youn, Jong Kyu; Hwang, Jae Hyeok [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Jeong, Ji-Heon; Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik, E-mail: wseum@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

2015-07-15

Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases. - Highlights: • Transduced Tat-CBR1 reduces LPS-induced inflammatory mediators and cytokines. • Tat-CBR1 inhibits MAPK and NF-κB activation. • Tat-CBR1 ameliorates inflammation response in vitro and in vivo. • Tat-CBR1 may be useful as potential therapeutic agent for inflammation.

Teacher Performance Assessment in Teacher Education: An Example in Malaysia

Science.gov (United States)

Gallant, Andrea; Mayer, Diane

2012-01-01

As part of a cross-cultural collaboration, a teacher performance assessment (TPA) was implemented during 2009 in three Malaysian institutes of teacher education. This paper reports on the TPA for graduating primary teachers in Malaysia. The investigation focused on the pre-service teachers' perceptions about whether the TPA provided them with an…

Characterization of tissue plasminogen activator binding proteins isolated from endothelial cells and other cell types

International Nuclear Information System (INIS)

Beebe, D.P.; Wood, L.L.; Moos, M.

1990-01-01

Human tissue plasminogen activator (t-PA) was shown to bind specifically to human osteosarcoma cells (HOS), and human epidermoid carcinoma cells (A-431 cells). Crosslinking studies with DTSSP demonstrated high molecular weight complexes (130,000) between 125 I-t-PA and cell membrane protein on human umbilical vein endothelial cells (HUVEC), HOS, and A-431 cells. A 48-65,000 molecular weight complex was demonstrated after crosslinking t-PA peptide (res. 7-20) to cells. Ligand blotting of cell lysates which had been passed over a t-PA affinity column revealed binding of t-PA to 54,000 and 95,000 molecular weight proteins. Several t-PA binding proteins were identified in immunopurified cell lysates, including tubulin beta chain, plasminogen activator inhibitor type 1 and single chain urokinase

Comparison of the bacterial removal performance of silver nanoparticles and a polymer based quaternary amine functiaonalized silsesquioxane coated point-of-use ceramic water filters.

Science.gov (United States)

Zhang, Hongyin; Oyanedel-Craver, Vinka

2013-09-15

This study compares the disinfection performance of ceramic water filters impregnated with two antibacterial compounds: silver nanoparticles and a polymer based quaternary amine functiaonalized silsesquioxane (poly(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride (TPA)). This study evaluated these compounds using ceramic disks manufactures with clay obtained from a ceramic filter factory located in San Mateo Ixtatan, Guatemala. Instead of using full size ceramic water filters, manufactured 6.5 cm diameter ceramic water filter disks were used. Results showed that TPA can achieve a log bacterial reduction value of 10 while silver nanoparticles reached up to 2 log reduction using a initial concentration of bacteria of 10(10)-10(11)CFU/ml. Similarly, bacterial transport demonstrated that ceramic filter disks painted with TPA achieved a bacterial log reduction value of 6.24, which is about 2 log higher than the values obtained for disks painted with silver nanoparticles (bacterial log reduction value: 4.42). The release of both disinfectants from the ceramic materials to the treated water was determined measuring the effluent concentrations in each test performed. Regarding TPA, about 3% of the total mass applied to the ceramic disks was released in the effluent over 300 min, which is slightly lower than the release percentage for silver nanoparticles (4%). This study showed that TPA provides a comparable disinfection performance than silver nanoparticles in ceramic water filter. Another advantage of using TPA is the cost as the price of TPA is considerable lower than silver nanoparticles. In spite of the use of TPA in several medical related products, there is only partial information regarding the health risk associated with the ingestion of this compound. Additional long-term toxicological information for TPA should be evaluated before its future application in ceramic water filters. Copyright © 2013 Elsevier B.V. All rights reserved.

Whole Genome Sequences of Three Treponema pallidum ssp. pertenue Strains: Yaws and Syphilis Treponemes Differ in Less than 0.2% of the Genome Sequence

Science.gov (United States)

Chen, Lei; Pospíšilová, Petra; Strouhal, Michal; Qin, Xiang; Mikalová, Lenka; Norris, Steven J.; Muzny, Donna M.; Gibbs, Richard A.; Fulton, Lucinda L.; Sodergren, Erica; Weinstock, George M.; Šmajs, David

2012-01-01

Background The yaws treponemes, Treponema pallidum ssp. pertenue (TPE) strains, are closely related to syphilis causing strains of Treponema pallidum ssp. pallidum (TPA). Both yaws and syphilis are distinguished on the basis of epidemiological characteristics, clinical symptoms, and several genetic signatures of the corresponding causative agents. Methodology/Principal Findings To precisely define genetic differences between TPA and TPE, high-quality whole genome sequences of three TPE strains (Samoa D, CDC-2, Gauthier) were determined using next-generation sequencing techniques. TPE genome sequences were compared to four genomes of TPA strains (Nichols, DAL-1, SS14, Chicago). The genome structure was identical in all three TPE strains with similar length ranging between 1,139,330 bp and 1,139,744 bp. No major genome rearrangements were found when compared to the four TPA genomes. The whole genome nucleotide divergence (dA) between TPA and TPE subspecies was 4.7 and 4.8 times higher than the observed nucleotide diversity (π) among TPA and TPE strains, respectively, corresponding to 99.8% identity between TPA and TPE genomes. A set of 97 (9.9%) TPE genes encoded proteins containing two or more amino acid replacements or other major sequence changes. The TPE divergent genes were mostly from the group encoding potential virulence factors and genes encoding proteins with unknown function. Conclusions/Significance Hypothetical genes, with genetic differences, consistently found between TPE and TPA strains are candidates for syphilitic treponemes virulence factors. Seventeen TPE genes were predicted under positive selection, and eleven of them coded either for predicted exported proteins or membrane proteins suggesting their possible association with the cell surface. Sequence changes between TPE and TPA strains and changes specific to individual strains represent suitable targets for subspecies- and strain-specific molecular diagnostics. PMID:22292095

Effect of oral administration of terephthalic acid on testicular functions of rats

International Nuclear Information System (INIS)

Cui Lunbiao; Dai Guidong; Xu Lichun; Wang Shouling; Song Ling; Zhao Renzhen; Xiao Hang; Zhou Jianwei; Wang Xinru

2004-01-01

To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats

Constructing Efficient and Stable Perovskite Solar Cells via Interconnecting Perovskite Grains.

Science.gov (United States)

Hou, Xian; Huang, Sumei; Ou-Yang, Wei; Pan, Likun; Sun, Zhuo; Chen, Xiaohong

2017-10-11

A high-quality perovskite film with interconnected perovskite grains was obtained by incorporating terephthalic acid (TPA) additive into the perovskite precursor solution. The presence of TPA changed the crystallization kinetics of the perovskite film and promoted lateral growth of grains in the vicinity of crystal boundaries. As a result, sheet-shaped perovskite was formed and covered onto the bottom grains, which made some adjacent grains partly merge together to form grains-interconnected perovskite film. Perovskite solar cells (PSCs) with TPA additive exhibited a power conversion efficiency (PCE) of 18.51% with less hysteresis, which is obviously higher than that of pristine cells (15.53%). PSCs without and with TPA additive retain 18 and 51% of the initial PCE value, respectively, aging for 35 days exposed to relative humidity 30% in air without encapsulation. Furthermore, MAPbI 3 film with TPA additive shows superior thermal stability to the pristine one under 100 °C baking. The results indicate that the presence of TPA in perovskite film can greatly improve the performance of PSCs as well as their moisture resistance and thermal stability.

Radiation induction of cancer of the skin

International Nuclear Information System (INIS)

Fry, R.J.M.; Storer, J.B.; Burns, F.J.

1985-01-01

The induction of epidermal tumors was studied using exposures to 25 kV x-rays with or without subsequent exposures to 12-0-tetradeconyl phorbol-13 acetate (TPA) or ultraviolet radiation (uvr) 280-400 nm. Fractionation regimens and total exposure up to 4000R produced no squamous cell carcinomas. When these regimes were followed by TPA an incidence of about 80% was obtained, and incidence of 60% when uvr exposures followed the x-irradiation. A dose-dependent increase in fibrosarcomas was found when x-irradiation was followed by 24 weeks of topical treatment with TPA. These results support the contention that uvr can enhance the expression of cells initiated by x-rays. The experimental evidence is compared with the data from the tinea capitis patients treated with x-rays. In C3HF/He male mice exposed to 50, 100, 150 and 200 rads 137 Cs gamma rays the induction rate for fibrosarcomas was 2.9 x 10 -4 per cGy/per mouse. This result compares with 2.5 x 10 -6 transformations per surviving cell per cGy with 10T1/2 cells that are fibroblasts derived from C3H mice. 16 refs., 1 fig., 1 tab

Theory of two-photon interactions with broadband down-converted light and entangled photons

International Nuclear Information System (INIS)

Dayan, Barak

2007-01-01

When two-photon interactions are induced by down-converted light with a bandwidth that exceeds the pump bandwidth, they can obtain a behavior that is pulselike temporally, yet spectrally narrow. At low photon fluxes this behavior reflects the time and energy entanglement between the down-converted photons. However, two-photon interactions such as two-photon absorption (TPA) and sum-frequency generation (SFG) can exhibit such a behavior even at high power levels, as long as the final state (i.e., the atomic level in TPA, or the generated light in SFG) is narrow-band enough. This behavior does not depend on the squeezing properties of the light, is insensitive to linear losses, and has potential applications. In this paper we describe analytically this behavior for traveling-wave down conversion with continuous or pulsed pumping, both for high- and low-power regimes. For this we derive a quantum-mechanical expression for the down-converted amplitude generated by an arbitrary pump, and formulate operators that represent various two-photon interactions induced by broadband light. This model is in excellent agreement with experimental results of TPA and SFG with high-power down-converted light and with entangled photons [Dayan et al., Phys. Rev. Lett. 93, 023005 (2004); 94, 043602 (2005); Pe'er et al., ibid. 94, 073601 (2005)

In vivo and in vitro expression of myeloid antigens on B-lineage acute lymphoblastic leukemia cells.

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Hara, J; Kawa-Ha, K; Yumura-Yagi, K; Kurahashi, H; Tawa, A; Ishihara, S; Inoue, M; Murayama, N; Okada, S

1991-01-01

The expression of myeloid antigens has been extensively examined using two-color analysis in 43 children with B-lineage acute lymphoblastic leukemia (ALL). On pre-culture cells, CD33 expression was frequently observed in CD19+, CD10- B-precursor ALL, and CD14 was expressed only on the cells from B-precursor ALL expressing CD19, CD10 and CD20, and B-ALL. After 2 or 3 days of culture without TPA, CD13 emerged on the cells from 21 of 29 patients irrespective of the presence or the absence of fetal calf serum in the culture. Of four patients with CD10+ B-precursor ALL, which showed no expression of CD13 after culture, two had T-cell associated antigens. Whereas the addition of TPA to the culture enhanced the expression of CD13 on the cells from acute non-lymphocytic leukemia (ANLL), TPA reduced the expression of this antigen on B-precursor cells. These findings suggest that the regulatory mechanism of CD13 expression may be different between B-precursor ALL and ANLL. Co-culture with cycloheximide mostly abrogated the induction of CD13, suggesting that CD13 expression was mainly dependent on de novo protein synthesis.

Unruptured Cerebral Aneurysm Detected after Intravenous Tissue Plasminogen Activator for Stroke

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Yukihiro Yoneda

2009-06-01

Full Text Available Therapeutic guidelines of intravenous thrombolysis with tissue plasminogen activator (tPA for hyperacute ischemic stroke are very strict. Because of potential higher risk of bleeding complications, the presence of unruptured cerebral aneurysm is a contraindication for systemic thrombolysis with tPA. According to the standard CT criteria, a 66-year-old woman who suddenly developed aphasia and hemiparesis received intravenous tPA within 3 h after ischemic stroke. Magnetic resonance angiography during tPA infusion was performed and the presence of a small unruptured cerebral aneurysm was suspected at the anterior communicating artery. Delayed cerebral angiography confirmed an aneurysm with a size of 7 mm. The patient did not experience any adverse complications associated with the aneurysm. Clinical experiences of this kind of accidental off-label thrombolysis may contribute to modify the current rigid tPA guidelines for stroke.

Resonant metallic nanostructure for enhanced two-photon absorption in a thin GaAs p-i-n diode

Energy Technology Data Exchange (ETDEWEB)

Portier, Benjamin; Pardo, Fabrice; Péré-Laperne, Nicolas; Steveler, Emilie; Dupuis, Christophe; Bardou, Nathalie; Lemaître, Aristide; Pelouard, Jean-Luc, E-mail: jean-luc.pelouard@lpn.cnrs.fr [Laboratoire de Photonique et de Nanostructures (LPN-CNRS), Route de Nozay, 91460 Marcoussis (France); Vest, Benjamin; Jaeck, Julien; Rosencher, Emmanuel [ONERA The French Aerospace Lab, Chemin de la Hunière, F-91760 Palaiseau (France); Haïdar, Riad [ONERA The French Aerospace Lab, Chemin de la Hunière, F-91760 Palaiseau (France); École Polytechnique, Département de Physique, F-91128 Palaiseau (France)

2014-07-07

Degenerate two-photon absorption (TPA) is investigated in a 186 nm thick gallium arsenide (GaAs) p-i-n diode embedded in a resonant metallic nanostructure. The full device consists in the GaAs layer, a gold subwavelength grating on the illuminated side, and a gold mirror on the opposite side. For TM-polarized light, the structure exhibits a resonance close to 1.47 μm, with a confined electric field in the intrinsic region, far from the metallic interfaces. A 109 times increase in photocurrent compared to a non-resonant device is obtained experimentally, while numerical simulations suggest that both gain in TPA-photocurrent and angular dependence can be further improved. For optimized grating parameters, a maximum gain of 241 is demonstrated numerically and over incidence angle range of (−30°; +30°).

Resonant metallic nanostructure for enhanced two-photon absorption in a thin GaAs p-i-n diode

International Nuclear Information System (INIS)

Portier, Benjamin; Pardo, Fabrice; Péré-Laperne, Nicolas; Steveler, Emilie; Dupuis, Christophe; Bardou, Nathalie; Lemaître, Aristide; Pelouard, Jean-Luc; Vest, Benjamin; Jaeck, Julien; Rosencher, Emmanuel; Haïdar, Riad

2014-01-01

Degenerate two-photon absorption (TPA) is investigated in a 186 nm thick gallium arsenide (GaAs) p-i-n diode embedded in a resonant metallic nanostructure. The full device consists in the GaAs layer, a gold subwavelength grating on the illuminated side, and a gold mirror on the opposite side. For TM-polarized light, the structure exhibits a resonance close to 1.47 μm, with a confined electric field in the intrinsic region, far from the metallic interfaces. A 109 times increase in photocurrent compared to a non-resonant device is obtained experimentally, while numerical simulations suggest that both gain in TPA-photocurrent and angular dependence can be further improved. For optimized grating parameters, a maximum gain of 241 is demonstrated numerically and over incidence angle range of (−30°; +30°).

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

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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.

12-O-Tetradecanoyl-phorbol-13-acetate and its relationship to SCE induction in Syrian and Chinese hamster cells

International Nuclear Information System (INIS)

Popescu, N.C.; Amsbaugh, S.C.; Larramendy, M.L.; DiPaolo

1982-01-01

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x-irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x-irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79-4 cells. Heat-inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first and second division post treatment on cells exposed to different 5-bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1-10μg/ml medium) and the number of cells divisions post treatment, TPA (0.01-2μg/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat-inactivated serum. Also, TPA did not increase the SCE frequency in V79-4 Chinese hamster cells cultured in heat-activated or noninactivated serum. Although SCE induction, a cellular response to carcinogen-induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alterations involved in SCE formation

Thrombin-specific inactivation of endothelial cell derived plasminogen activator

International Nuclear Information System (INIS)

Highsmith, R.F.; Gallaher, M.J.

1986-01-01

Although thrombin (T) has diverse functions in the overall hemostatic mechanism, relatively little is known about its direct effect on components of the fibrinolytic enzyme system. The authors have investigated the interaction of T with plasminogen activators (PA) derived from bovine aortic endothelial cells (EC) in culture (2-5th passage, preconfluent monolayers). Varying concentrations of purified bovine or human thrombin were added to EC-conditioned media (CM). CM + T mixtures were assayed at various times for PA activity using purified plasminogen and a sensitive 125 I-fibrinogenolytic or caseinolytic assay. T (5 nM), but not plasmin or trypsin at equivalent concentrations, resulted in a time-dependent inhibition of the PA activity in CM. T had no effect on the PA activity of urokinase, streptokinase or preformed plasmin. The ability of T to inactivate the EC-derived PA was abolished by prior treatment of T with active site-directed reagents. SDS-PAGE and zymography with copolymerized fibrinogen and plasminogen revealed further specificity in that only one of the multiple-molecular weight forms of PA present in EC-CM was inactivated by T. The authors conclude that in a highly specific fashion, T inactivates the predominant PA present in EC-CM by limited proteolysis. Thus, another potentially important function of T is suggested which may have particular significance in the temporal regulation of coagulation and fibrinolysis at the blood-endothelium interface

Identification and phylogenetic analysis of Tityus pachyurus and Tityus obscurus novel putative Na+-channel scorpion toxins.

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Jimmy A Guerrero-Vargas

Full Text Available Colombia and Brazil are affected by severe cases of scorpionism. In Colombia the most dangerous accidents are caused by Tityus pachyurus that is widely distributed around this country. In the Brazilian Amazonian region scorpion stings are a common event caused by Tityus obscurus. The main objective of this work was to perform the molecular cloning of the putative Na(+-channel scorpion toxins (NaScTxs from T. pachyurus and T. obscurus venom glands and to analyze their phylogenetic relationship with other known NaScTxs from Tityus species.cDNA libraries from venom glands of these two species were constructed and five nucleotide sequences from T. pachyurus were identified as putative modulators of Na(+-channels, and were named Tpa4, Tpa5, Tpa6, Tpa7 and Tpa8; the latter being the first anti-insect excitatory β-class NaScTx in Tityus scorpion venom to be described. Fifteen sequences from T. obscurus were identified as putative NaScTxs, among which three had been previously described, and the others were named To4 to To15. The peptides Tpa4, Tpa5, Tpa6, To6, To7, To9, To10 and To14 are closely related to the α-class NaScTxs, whereas Tpa7, Tpa8, To4, To8, To12 and To15 sequences are more related to the β-class NaScTxs. To5 is possibly an arthropod specific toxin. To11 and To13 share sequence similarities with both α and β NaScTxs. By means of phylogenetic analysis using the Maximum Parsimony method and the known NaScTxs from Tityus species, these toxins were clustered into 14 distinct groups.This communication describes new putative NaScTxs from T. pachyurus and T. obscurus and their phylogenetic analysis. The results indicate clear geographic separation between scorpions of Tityus genus inhabiting the Amazonian and Mountain Andes regions and those distributed over the Southern of the Amazonian rainforest. Based on the consensus sequences for the different clusters, a new nomenclature for the NaScTxs is proposed.

Drivers of costs associated with reperfusion therapy in acute stroke: the Interventional Management of Stroke III Trial.

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Simpson, Kit N; Simpson, Annie N; Mauldin, Patrick D; Hill, Michael D; Yeatts, Sharon D; Spilker, Judith A; Foster, Lydia D; Khatri, Pooja; Martin, Renee; Jauch, Edward C; Kleindorfer, Dawn; Palesch, Yuko Y; Broderick, Joseph P

2014-06-01

The Interventional Management of Stroke (IMS) III study tested the effect of intravenous tissue-type plasminogen activator (tPA) alone when compared with intravenous tPA followed by endovascular therapy and collected cost data to assess the economic implications of the 2 therapies. This report describes the factors affecting the costs of the initial hospitalization for acute stroke subjects from the United States. Prospective cost analysis of the US subjects was treated with intravenous tPA alone or with intravenous tPA followed by endovascular therapy in the IMS III trial. Results were compared with expected Medicare payments. The adjusted cost of a stroke admission in the study was $35 130 for subjects treated with endovascular therapy after intravenous tPA treatment and $25 630 for subjects treated with intravenous tPA alone (P<0.0001). Significant factors related to costs included treatment group, baseline National Institutes of Health Stroke Scale, time from stroke onset to intravenous tPA, age, stroke location, and comorbid diabetes mellitus. The mean cost for subjects who had routine use of general anesthesia as part of endovascular therapy was $46 444 when compared with $30 350 for those who did not have general anesthesia. The costs of embolectomy for IMS III subjects and patients from the National Inpatient Sample cohort exceeded the Medicare diagnosis-related group payment in ≥75% of patients. Minimizing the time to start of intravenous tPA and decreasing the use of routine general anesthesia may improve the cost-effectiveness of medical and endovascular therapy for acute stroke. http://www.clinicaltrials.gov. Unique identifier: NCT00359424. © 2014 American Heart Association, Inc.

Effect of the transpalatal arch during extraction treatment.

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Zablocki, Heather L; McNamara, James A; Franchi, Lorenzo; Baccetti, Tiziano

2008-06-01

The transpalatal arch (TPA) can be used as an adjunct during orthodontic treatment to help control the movement of the maxillary first molars in 3 dimensions, including producing molar rotation and uprighting, maintaining transverse dimensions posteriorly during treatment, and maintaining leeway spaces during the transition of the dentition. The purpose of this retrospective cephalometric study was to test an additional function of the TPA: its ability to enhance orthodontic anchorage during extraction treatment. Records consisting of pretreatment and posttreatment cephalograms were gathered from several orthodontic practices that used an .018 x .025-in preangulated appliance. All patients were white and had 4 first premolars extracted as part of their treatment protocol. Patients were treated either with or without a TPA of the soldered Goshgarian design. Patients were excluded if headgear or any other auxiliary anchorage device beside the TPA was used during treatment. Matched samples of 30 patients were identified based on sex, age at the start of treatment, treatment duration, and cervical vertebral maturation stage. Statistical comparisons were made with nonparametric statistical tests. Analysis of the changes from pretreatment to posttreatment for the TPA and the no-TPA groups showed no statistically significant differences in any of the variables examined. The net difference for both vertical and mesial movement of the maxillary first molar in relation to the maxilla between the 2 groups was 0.4 mm, with the no-TPA group in a more downward and forward position. Although the usefulness of the TPA for the abovementioned functions is not negated, it does not provide a significant effect on either the anteroposterior or the vertical position of the maxillary first molars during extraction treatment.

Combination therapy with normobaric oxygen (NBO plus thrombolysis in experimental ischemic stroke

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Singhal Aneesh B

2009-07-01

Full Text Available Abstract Background The widespread use of tissue plasminogen activator (tPA, the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy. Results Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100% and smaller infarct volumes (379 ± 57 mm3 saline controls; 309 ± 58 mm3 NBO; 201 ± 78 mm3 tPA; 138 ± 30 mm3 tPA plus NBO, showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality. Conclusion NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation.

Isolation of an X-ray-responsive element in the promoter region of tissue-type plasminogen activator: Potential uses of X-ray-responsive elements for gene therapy

International Nuclear Information System (INIS)

Boothman, D.A.; Lee, I.W.; Sahijdak, W.M.

1994-01-01

Tissue-type plasminogen activator (t-PA) was induced over 50-fold after X irradiation in radioresistant human melanoma cells. Activities of t-PA were induced 14-fold in ataxia telangiectasia, 9-fold in Bloom's syndrome and 6-fold in Fanconi's anemia cells, compared to normal human fibroblasts. X-ray-inducible synthesis of the protease, t-PA, may play a role(s) in damage-inducible repair processes in mammalian cells, similar to the SOS repair systems in lower eukaryotes and prokaryotes. DNA band shift and DNase I footprinting assays were used to determine binding if transcription factors to a previously unknown X-ray-responsive element (XRE) in the t-PA promoter. The major goals of our research with XREs are to understand (a) which transcription factor(s) regulates to-PA induction after X-rays, and (b) the role(s) of t-PA in DNA repair, apoptosis or other responses to X rays. The purpose of this paper is to discuss the potential use of an XRE, such as the one in the t-PA promoter, for gene radiotherapy. Several gene therapy strategies are proposed. 22 refs., 3 figs

Three coordination polymers constructed from 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid: Synthesis, crystal structure and properties

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Zhai, Dandan; Sun, Wujuan; Fan, Fei; Liao, Xuzhao; Chen, Sanping; Yang, Xuwu

2017-04-01

Three new coordination polymers, namely, {[Co2(TPA)(μ3-O)3]·0.5DMA}n (1), {[Co(H2TPA)(bibp)(H2O)3]·H2O}n (2) and {[Cd3(TPA)2(phen)4]·4H2O}n (3), (H3TPA = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid, bibp = 4,4'-bis(imidazolyl)biphenyl, phen = 1,10-phenanthroline and DMA = N,N-dimethylacetamide), have been synthesized under solvothermal conditions and structurally characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction analysis. Polymer 1 exhibits a three-dimensional (3D) structure constructed from 5-connected secondary building units (SBUs) [Co3(μ3-O)] and 3-connected H3TPA ligands. Polymer 2 has a 1D zigzag polymer chain connected by H3TPA and bibp ligands. Polymer 3 features an unusual 3D framework with a (3,4,2)-connected {4; 6;8}{4; 62;83} topology. Moreover, the thermal stabilities of 1-3 and photoluminescence properties of 3 have been investigated. Magnetic susceptibility measurements indicate that polymers 1-2 display antiferromagnetic exchange properties.

Psychophysical evaluation of a variable friction tactile interface

Science.gov (United States)

Samur, Evren; Colgate, J. Edward; Peshkin, Michael A.

2009-02-01

This study explores the haptic rendering capabilities of a variable friction tactile interface through psychophysical experiments. In order to obtain a deeper understanding of the sensory resolution associated with the Tactile Pattern Display (TPaD), friction discrimination experiments are conducted. During the experiments, subjects are asked to explore the glass surface of the TPaD using their bare index fingers, to feel the friction on the surface, and to compare the slipperiness of two stimuli, displayed in sequential order. The fingertip position data is collected by an infrared frame and normal and translational forces applied by the finger are measured by force sensors attached to the TPaD. The recorded data is used to calculate the coefficient of friction between the fingertip and the TPaD. The experiments determine the just noticeable difference (JND) of friction coefficient for humans interacting with the TPaD.

Broadband two-photon absorption cross sections of benzothiazole derivatives and benzobisthiazolium salts

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Noskovičova, Eva; Lorenc, Dušan; Magdolen, Peter; Sigmundová, Ivica; Zahradník, Pavol; Velič, Dušan

2018-05-01

Two-photon absorption (TPA) cross sections of conjugated donor-π-acceptor dipolar structures containing benzothiazole or benzobisthiazolium moieties are determined in a broad spectral range from 700 nm to 1000 nm using two-photon induced fluorescence technique. The TPA cross section values range from 150 GM to 4600 GM. The largest values are observed in near-infrared region. The dipolar derivative of benzothiazole has the largest TPA cross section of 4600 GM at wavelength of 890 nm. A combination of the large TPA in the near-infrared region and the high emission quantum yield makes these compounds excellent candidates for two-photon fluorescence microscopy.

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

Science.gov (United States)

Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

2015-10-22

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Diferencias cinéticas de las plasminas de ocho especies mamíferas: activaciones y secuencias de los terminales-N

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Omaira Cañás Bermúdez

2013-12-01

Full Text Available El artículo determina los parámetros cinéticos de las plasminas de ocho especies de mamíferos y sus terminales-N. Los ocho plasminógenos fueron purificados por los mismos métodos (cromatografías de afinidad e intercambio iónico, y activados con urocinasa, partiendo de una concentración común y su cinética valorada según las coordenadas de Lineweaver- Burk. Para esto se utilizó la cinética enzimática de Michaelis Menten, ampliamente usada en el estudio de enzimas. Todos los plasminógenos mostraron una pureza superior al 95 % y una banda de 92 kDa en la electroforesis, al comparar con el estándar de peso molecular utilizado. Las plasminas del equino y canino mostraron la misma KM por el sustrato cromogénico (0,438 mM, siendo esta la de mayor afinidad en este estudio y la humana la de menor afinidad (5,3 mM. También fueron determinadas la constante catalítica y la velocidad de conversión del sustrato cromogénico a producto. Los terminales-N de los plasminógenos de las ocho especies fueron determinados, y se encontraron diferencias entre el humano y los animales; así mismo entre algunos animales. Solo el porcino y el ovino no mostraron diferencia alguna en su terminal-N (DPPDDY. Se demostró la unificación del método de purificación de los plasminógenos para cualquier especie, las diferencias cinéticas de las ocho plasminas estudiadas, y las similitudes y diferencias en la secuencia de los terminales-N de las ocho especies.

Resonant two-photon absorption and electromagnetically induced transparency in open ladder-type atomic system.

Science.gov (United States)

Moon, Han Seb; Noh, Heung-Ryoul

2013-03-25

We have experimentally and theoretically studied resonant two-photon absorption (TPA) and electromagnetically induced transparency (EIT) in the open ladder-type atomic system of the 5S(1/2) (F = 1)-5P(3/2) (F' = 0, 1, 2)-5D(5/2) (F″ = 1, 2, 3) transitions in (87)Rb atoms. As the coupling laser intensity was increased, the resonant TPA was transformed to EIT for the 5S(1/2) (F = 1)-5P(3/2) (F' = 2)-5D(5/2) (F″ = 3) transition. The transformation of resonant TPA into EIT was numerically calculated for various coupling laser intensities, considering all the degenerate magnetic sublevels of the 5S(1/2)-5P(3/2)-5D(5/2) transition. From the numerical results, the crossover from TPA to EIT could be understood by the decomposition of the spectrum into an EIT component owing to the pure two-photon coherence and a TPA component caused by the mixed term.

Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity.

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Takayama, S; White, M F; Kahn, C R

1988-03-05

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the function of the insulin receptor was examined in intact hepatoma cells (Fao) and in solubilized extracts purified by wheat germ agglutinin chromatography. Incubation of ortho[32P]phosphate-labeled Fao cells with TPA increased the phosphorylation of the insulin receptor 2-fold after 30 min. Analysis of tryptic phosphopeptides from the beta-subunit of the receptor by reverse-phase high performance liquid chromatography and determination of their phosphoamino acid composition suggested that TPA predominantly stimulated phosphorylation of serine residues in a single tryptic peptide. Incubation of the Fao cells with insulin (100 nM) for 1 min stimulated 4-fold the phosphorylation of the beta-subunit of the insulin receptor. Prior treatment of the cells with TPA inhibited the insulin-stimulated tyrosine phosphorylation by 50%. The receptors extracted with Triton X-100 from TPA-treated Fao cells and purified on immobilized wheat germ agglutinin retained the alteration in kinase activity and exhibited a 50% decrease in insulin-stimulated tyrosine autophosphorylation and phosphotransferase activity toward exogenous substrates. This was due primarily to a decrease in the Vmax for these reactions. TPA treatment also decreased the Km of the insulin receptor for ATP. Incubation of the insulin receptor purified from TPA-treated cells with alkaline phosphatase decreased the phosphate content of the beta-subunit to the control level and reversed the inhibition, suggesting that the serine phosphorylation of the beta-subunit was responsible for the decreased tyrosine kinase activity. Our results support the notion that the insulin receptor is a substrate for protein kinase C in the Fao cell and that the increase in serine phosphorylation of the beta-subunit of the receptor produced by TPA treatment inhibited tyrosine kinase activity in vivo and in vitro. These data suggest that protein kinase C may regulate the function

Exploring a new quantitative image marker to assess benefit of chemotherapy to ovarian cancer patients

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Mirniaharikandehei, Seyedehnafiseh; Patil, Omkar; Aghaei, Faranak; Wang, Yunzhi; Zheng, Bin

2017-03-01

Accurately assessing the potential benefit of chemotherapy to cancer patients is an important prerequisite to developing precision medicine in cancer treatment. The previous study has shown that total psoas area (TPA) measured on preoperative cross-section CT image might be a good image marker to predict long-term outcome of pancreatic cancer patients after surgery. However, accurate and automated segmentation of TPA from the CT image is difficult due to the fuzzy boundary or connection of TPA to other muscle areas. In this study, we developed a new interactive computer-aided detection (ICAD) scheme aiming to segment TPA from the abdominal CT images more accurately and assess the feasibility of using this new quantitative image marker to predict the benefit of ovarian cancer patients receiving Bevacizumab-based chemotherapy. ICAD scheme was applied to identify a CT image slice of interest, which is located at the level of L3 (vertebral spines). The cross-sections of the right and left TPA are segmented using a set of adaptively adjusted boundary conditions. TPA is then quantitatively measured. In addition, recent studies have investigated that muscle radiation attenuation which reflects fat deposition in the tissue might be a good image feature for predicting the survival rate of cancer patients. The scheme and TPA measurement task were applied to a large national clinical trial database involving 1,247 ovarian cancer patients. By comparing with manual segmentation results, we found that ICAD scheme could yield higher accuracy and consistency for this task. Using a new ICAD scheme can provide clinical researchers a useful tool to more efficiently and accurately extract TPA as well as muscle radiation attenuation as new image makers, and allow them to investigate the discriminatory power of it to predict progression-free survival and/or overall survival of the cancer patients before and after taking chemotherapy.

TUNGSTOPHOSPHORIC ACID HETEROGENIZED ONTO NH4ZSM5 AS AN EFFICIENT AND RECYCLABLE CATALYST FOR THE PHOTOCATALYTIC DEGRADATION OF DYES

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Candelaria Leal Marchena

2015-05-01

Full Text Available Materials based on tungstophosphoric acid (TPA immobilized on NH4ZSM5 zeolite were prepared by wet impregnation of the zeolite matrix with TPA aqueous solutions. Their concentration was varied in order to obtain TPA contents of 5%, 10%, 20%, and 30% w/w in the solid. The materials were characterized by N2 adsorption-desorption isotherms, XRD, FT-IR, 31P MAS-NMR, TGA-DSC, DRS-UV-Vis, and the acidic behavior was studied by potentiometric titration with n-butylamine. The BET surface area (SBET decreased when the TPA content was raised as a result of zeolite pore blocking. The X-ray diffraction patterns of the solids modified with TPA only presented the characteristic peaks of NH4ZSM5 zeolites, and an additional set of peaks assigned to the presence of (NH43PW12O40. According to the Fourier transform infrared and 31P magic angle spinning-nuclear magnetic resonance spectra, the main species present in the samples was the [PW12O40]3- anion, which was partially transformed into the [P2W21O71]6- anion during the synthesis and drying steps. The thermal stability of the NH4ZSM5TPA materials was similar to that of their parent zeolites. Moreover, the samples with the highest TPA content exhibited band gap energy values similar to those reported for TiO2. The immobilization of TPA on NH4ZSM5 zeolite allowed the obtention of catalysts with high photocatalytic activity in the degradation of methyl orange dye (MO in water, at 25 ºC. These can be reused at least three times without any significant decrease in degree of degradation.

Sectional microprocessor based microcomputer and its application to express analysis using interactive language

International Nuclear Information System (INIS)

Lang, I.; Leveleki, L.; Salai, M.; Turani, D.

1984-01-01

Sectional microprocessor TPA-L/128H based mini-computer being a part of the TPA-8 computer family is developed. A substantial increase of the computer operation rate is attained at the expense of microprogram monitoring. The central processor is constructed on the base of the AM2900 sectional microprocessor elements. The TPA-L/128H computer is program compatible with TPA-8 computer, perfectly equipped with software: high level languages as well as OS/L, COS/H, RTS/H, PAL/128, WPS, TEASYS-8 and IL 128 ensuring statistical data processing, physical experiments automation and interactive experimental data processing. The real time basis problems and CAMAC devices monitoring are efficiently solved

Chemopreventive and Anticancer Activities of Allium victorialis var. platyphyllum Extracts.

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Kim, Hyun-Jeong; Park, Min Jeong; Park, Hee-Juhn; Chung, Won-Yoon; Kim, Ki-Rim; Park, Kwang-Kyun

2014-09-01

Allium victorialis var. platyphyllum is an edible perennial herb and has been used as a vegetable or as a Korean traditional medicine. Allium species have received much attention owing to their diverse pharmacological properties, including antioxidative, anti-inflammatory, and anticancer activities. However, A. victorialis var. platyphyllum needs more study. The chemopreventive potential of A. victorialis var. platyphyllum methanol extracts was examined by measuring 12-O-tetra-decanoylphorbol 13-acetate (TPA)-induced superoxide anion production in the differentiated HL-60 cells, TPA-induced mouse ear edema, and Ames/Salmonella mutagenicity. The apoptosis-inducing capabilities of the extracts were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, 4',6-diamidino-2-phenylindole staining, and the DNA fragmentation assay in human colon cancer HT-29 cells. Antimetastatic activities of the extracts were also investigated in an experimental mouse lung metastasis model. The methanol extracts of A. victorialis var. platyphyllum rhizome (AVP-R) and A. victorialis var. platyphyllum stem (AVP-S) dose-dependently inhibited the TPA-induced generation of superoxide anion in HL-60 cells and TPA-induced ear edema in mice, as well as 7,12-dimethylbenz[a]anthracene (DMBA) and tert-butyl hydroperoxide (t-BOOH) -induced bacterial mutagenesis. AVP-R and AVP-S reduced cell viability in a dose-related manner and induced apoptotic morphological changes and internucleosomal DNA fragmentation in HT-29 cells. In the experimental mouse lung metastasis model, the formation of tumor nodules in lung tissue was significantly inhibited by the treatment of the extracts. AVP-R and AVP-S possess antioxidative, anti-inflammatory, antimutagenic, proapoptotic, and antimetastatic activities. Therefore, these extracts can serve as a beneficial supplement for the prevention and treatment of cancer.

Phorbol ester tumor promoter induced the synthesis of two major cytoplasmic proteins: identity with two proteins induced under heat-shocked and glucose-starved conditions

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Zhang, H.; Chen, K.Y.; Liu, A.Y.C.

1987-01-01

The regulation of specific protein synthesis by the phorbol ester tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was evaluated using the L-8 and C-2 myoblast and the 3T3-L1 fibroblast cell cultures. TPA increased, by 2-4 fold, the synthesis rates of two cytoplasmic proteins with apparent molecular weights of 89,000 and 74,000 as determined by SDS-polyacrylamide gel electrophoresis and autoradiography. The concentration of TPA and the time of incubation needed to elicit this induction was determined to be 10 μg/ml and 20 hrs, respectively. Increasing the concentration of TPA to 100, 200, and 500 ng/ml did not result in a greater magnitude of induction. The possibility that these two TPA-induced proteins may be identical to proteins with similar molecular weights induced under heat-shocked or glucose-starved conditions was evaluated by 1-D and 2-D gel electrophoresis and autoradiography. Results provided evidence that the TPA-induced 89,000- and 74,000-dalton proteins were identical to hsp 89 and hsp 74, 2 out of a set of 8-9 proteins induced under heat shocked conditions. Furthermore, they are identical to two of the set of glucose-regulated proteins induced under a glucose-starved condition

Protective effect of topical application of α-tocopherol and/or N-acetyl cysteine on argemone oil/alkaloid-induced skin tumorigenesis in mice.

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Pal, Anu; Alam, Shamshad; Singhal, Jaya; Kumar, Rahul; Ansari, Kausar M; Das, Mukul

2013-01-01

Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.

Correction to: Generation and characterization of tissue-type plasminogen activator transgenic rats.

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Ito, Yusuke; Noguchi, Kengo; Morishima, Yoshiyuki; Yamaguchi, Kyoji

2018-01-01

In the original publication of the article, the sentence in "Result" section have been incorrectly published as: "Three lines of tPA Tg rats were generated and analyzed by Southern blotting to confirm the presence of the transgene in genomic DNA. When rat DNA was digested with EcoRI and hybridized to the tPA probe described in "Materials and methods", a 1.0 kb band was detected (Fig. 1a, b). One founder line was selected because of its high copy number (about ten copies) of tPA gene and itansgene) and 4.4 kb (endogenous gene) reding appearance, body weight, hematology, and systematization." The corrected sentence should read as: "Three lines of tPA Tg rats were generated and analyzed by Southern blotting to confirm the presence of the transgene in genomic DNA. When rat DNA was digested with EcoRI and hybridized to the tPA probe described in "Materials and methods", a 1.0 kb band was detected (Fig. 1a, b). One founder line was selected because of its high copy number (about ten copies) of tPA gene and its lack of detectable abnormal findings, including appearance, body weight, hematology, and systematization." The original article has been corrected.

Spatial and social factors associated with transportation and recreational physical activity among adults in Hat Yai City, Songkhla,Thailand.

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Churangsarit, Saowaphan; Chongsuvivatwong, Virasakdi

2011-08-01

Transportation physical activity (TPA) and recreational physical activity (RPA) in an urban area can be sources of physical activity (PA) in addition to working. This study was conducted in Hat Yai City Municipality, the fourth most populous city in Thailand, to describe the magnitude of these physical activities and identify their associated factors. 369 adults were selected from a random sampling of registered households. Based on the Global Physical Activity Questionnaire (GPAQ), subjects were interviewed on their modes of TPA and RPA during the past week. Hurdle regression was used to examine predictors for having PA separately from predictor of intensity of PA among the active. Metabolic equivalent (MET) of TPA and RPA were computed. Prevalence of not having TPA and RPA were 71.3% and 45.8%, respectively. TPA and RPA contributed 1.5% and 9.2% of total PA. Active commuters were more common in females 40 or more years old, less sedentary persons, and those living near shopping places. Persons having RPA were more likely to be less sedentary, whereas the intensity of RPA was higher among single persons and males. TPA and RPA in this study area were uncommon. Further strategies are needed to improve the situation, especially among sedentary persons.

Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats

International Nuclear Information System (INIS)

Deaciuc, I.V.; Spitzer, J.A.

1989-01-01

The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis

Exercise Activates p53 and Negatively Regulates IGF-1 Pathway in Epidermis within a Skin Cancer Model.

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Yu, Miao; King, Brenee; Ewert, Emily; Su, Xiaoyu; Mardiyati, Nur; Zhao, Zhihui; Wang, Weiqun

2016-01-01

Exercise has been previously reported to lower cancer risk through reducing circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model. This study aims to investigate the underlying mechanisms by which exercise may down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10-week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were topically treated with TPA 2 hours before sacrifice and the target proteins in the epidermis were analyzed by both immunohistochemistry and Western blot. Under TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised mice when compared with sedentary control. Meanwhile, p53 was significantly elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and PTEN, increased in response to exercise. There was a synergy effect between exercise and TPA on the decreased MDM2 and increased p53, but not p53-transcripted proteins. Taken together, exercise appeared to activate p53, resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a negative regulation of IGF-1 pathway and thus contribute to the observed cancer prevention by exercise in this skin cancer model.

The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease

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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.

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)

Endovascular Mechanical Thrombectomy in Large-Vessel Occlusion Ischemic Stroke Presenting with Low National Institutes of Health Stroke Scale: Systematic Review and Meta-Analysis.

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Griessenauer, Christoph J; Medin, Caroline; Maingard, Julian; Chandra, Ronil V; Ng, Wyatt; Brooks, Duncan Mark; Asadi, Hamed; Killer-Oberpfalzer, Monika; Schirmer, Clemens M; Moore, Justin M; Ogilvy, Christopher S; Thomas, Ajith J; Phan, Kevin

2018-02-01

Mechanical thrombectomy has become the standard of care for management of most large vessel occlusion (LVO) strokes. When patients with LVO present with minor stroke symptomatology, no consensus on the role of mechanical thrombectomy exists. A systematic review and meta-analysis were performed to identify studies that focused on mechanical thrombectomy, either as a standalone treatment or with intravenous tissue plasminogen activator (IV tPA), in patients with mild strokes with LVO, defined as a baseline National Institutes of Health Stroke Scale score ≤5 at presentation. Data on methodology, quality criteria, and outcome measures were extracted, and outcomes were compared using odds ratio as a summary statistic. Five studies met the selection criteria and were included. When compared with medical therapy without IV tPA, mechanical thrombectomy and medical therapy with IV tPA were associated with improved 90-day modified Rankin Scale (mRS) score. Among medical patients who were not eligible for IV tPA, those who underwent mechanical thrombectomy were more likely to experience good 90-day mRS than those who were not. There was no significant difference in functional outcome between mechanical thrombectomy and medical therapy with IV tPA, and no treatment subgroup was associated with intracranial hemorrhage or death. In patients with mild strokes due to LVO, mechanical thrombectomy and medical therapy with IV tPA led to better 90-day functional outcome. Mechanical thrombectomy plays an important role in the management of these patients, particularly in those not eligible for IV tPA. Copyright © 2017 Elsevier Inc. All rights reserved.

Endovascular Therapy is Effective and Safe for Patients with Severe Ischemic Stroke: Pooled Analysis of IMS III and MR CLEAN Data

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Broderick, Joseph P.; Berkhemer, Olvert A.; Palesch, Yuko Y.; Dippel, Diederik W.J.; Foster, Lydia D.; Roos, Yvo B.W.E.M.; van der Lugt, Aad; Tomsick, Thomas A.; Majoie, Charles B.L.M.; van Zwam, Wim H.; Demchuk, Andrew M.; van Oostenbrugge, Robert J.; Khatri, Pooja; Lingsma, Hester F.; Hill, Michael D.; Roozenbeek, Bob; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig S.; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Kit

2015-01-01

Background and Purpose We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (NIHSS ≥20) following a pre-specified analysis plan. Methods The pooled analysis of the IMS III and MR CLEAN trial included participants with an NIHSS ≥20 prior to intravenous (IV) t-PA treatment (IMS III) or randomization (MR CLEAN) who were treated with IV t-PA ≤ 3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy following IV t-PA would have improved 90-day outcome (distribution of modified Rankin scale [mRS] scores), as compared to those who received IV t-PA alone. Results Among 342 participants in the pooled analysis (194 from IMS III, 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared to the IV t-PA group (adjusted odds ratio [aOR] 1.78; 95% confidence interval [CI] 1.20-2.66). In the logistic regression model of the dichotomous outcome (mRS 0-2, or ‘functional independence’), the endovascular group had superior outcomes (aOR 1.97; 95% CI 1.09-3.56). Functional independence (mRS ≤2) at 90 days was 25% in the endovascular group as compared to 14% in the IV t-PA group. Conclusions Endovascular therapy following IV t-PA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. PMID:26486865

Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

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Lipigorngoson Suwiwek

2001-01-01

Full Text Available Abstract Background We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(aanthracene (DMBA-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Results Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham. Conclusions Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin.

Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

International Nuclear Information System (INIS)

Limtrakul, Porn-ngarm; Anuchapreeda, Songyot; Lipigorngoson, Suwiwek; Dunn, Floyd W

2001-01-01

We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham). Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin

Synthesis and Verification of Biobased Terephthalic Acid from Furfural

Science.gov (United States)

Tachibana, Yuya; Kimura, Saori; Kasuya, Ken-Ichi

2015-02-01

Exploiting biomass as an alternative to petrochemicals for the production of commodity plastics is vitally important if we are to become a more sustainable society. Here, we report a synthetic route for the production of terephthalic acid (TPA), the monomer of the widely used thermoplastic polymer poly(ethylene terephthalate) (PET), from the biomass-derived starting material furfural. Biobased furfural was oxidised and dehydrated to give maleic anhydride, which was further reacted with biobased furan to give its Diels-Alder (DA) adduct. The dehydration of the DA adduct gave phthalic anhydride, which was converted via phthalic acid and dipotassium phthalate to TPA. The biobased carbon content of the TPA was measured by accelerator mass spectroscopy and the TPA was found to be made of 100% biobased carbon.

How do 10-camphorsulfonic acid, silver or aluminum nanoparticles influence optical, electrochemical, electrochromic and photovoltaic properties of air and thermally stable triphenylamine-based polyazomethine with carbazole moieties?

International Nuclear Information System (INIS)

Iwan, Agnieszka; Boharewicz, Bartosz; Tazbir, Igor; Filapek, Michal; Korona, Krzysztof P.; Wróbel, Piotr; Stefaniuk, Tomasz; Ciesielski, Arkadiusz; Wojtkiewicz, Jacek; Wronkowska, Aleksandra A.; Wronkowski, Andrzej; Zboromirska-Wnukiewicz, Beata; Grankowska-Ciechanowicz, Sylwia; Kaminska, Maria; Szoplik, Tomasz

2015-01-01

Organic (10-camphorsulfonic acid, CSA), organic-inorganic (Ag-poly(vinylpyrrolidone), Ag-PVP with 10 and 20 nm size of Ag) or inorganic (Al, 18 nm) compounds were applied as new components of active layer in bulk heterojunction polymer solar cells based on a new polyazomethine (PAZ-Car-TPA) resulting in significant change of optical and electrical properties. Moreover, colloidal Ag (100 nm) and Ag-PVP in aqueous solution (10 nm) were tested as an addition to the hole transporting layer based on PEDOT:PSS in polyazomethine solar cells. CSA added to PAZ-Car-TPA decrease its energy gap from 1.91 to 1.20 eV and causes a significant bathochromic shift of the maximum of absorption band along with the change of the polymer color from yellow to red (electrochromic behavior). Photoluminescence maximum of PAZ-Car-TPA protonated with CSA showed 120 nm redshift from 500 to 620 nm in comparison to undoped PAZ-Car-TPA. HOMO-LUMO of PAZ-Car-TPA and its mixture with CSA were analyzed by cyclic voltammetry and quantum mechanical calculations using Density Functional Theory method. Refraction index and extinction coefficient of PAZ-Car-TPA and its mixtures with PC 71 BM as well as Ag or Al nanoparticles were investigated taking into consideration various thickness of polymer layer. The power conversion efficiency of the ITO/PEDOT:PSS/PAZ-Car-TPA:PCBM:CSA/Al device was five time higher than that of the device based on PAZ-Car-TPA:PCBM. Such an enhancement was found to be primarily due to the increase of the short-circuit current, suggesting that the charge collection increases upon the incorporation of CSA in the active layer. Moreover, presence of Ag-PVP (20 nm) or Al (18 nm) in device increased short circuit current of the constructed polymer solar cells. Additionally, devices were tested by external quantum efficiency measurements and electrochemical impedance spectroscopy in dark and under illumination. The polymer solar cell with PAZ-Car-TPA as donor in active layer showed good

Exposure to asbestos and levels of selected tumor biomarkers

International Nuclear Information System (INIS)

Krajewska, B.; Lutz, W.; Pilacik, B.

1996-01-01

Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify

Influence of bradykinin on diacylglycerol and phosphatidic acid accumulation in cultured bovine adrenal chromaffin cells.

Science.gov (United States)

Owen, P J; Boarder, M R

1991-09-01

Earlier studies have shown that bradykinin stimulated release of catecholamines from chromaffin cells by an influx of calcium through dihydropyridine-insensitive channels, and also that bradykinin stimulated (poly)phosphoinositide hydrolysis. To investigate membrane-bound second messengers in chromaffin cells, and to elucidate any role these may play in stimulus-secretion coupling, we have studied the influence of bradykinin on diacylglycerol and phosphatidic acid (PA). Using equilibrium labelling of primary cultures of chromaffin cells with [3H]arachidonic acid or [3H]glycerol, we found no influence of bradykinin (10 nM) on labelled diacylglycerol formation, either in the presence or absence of inhibitors of diacylglycerol lipase or kinase. However, when we used cells prelabelled with 32Pi for 2.5 h, we found that bradykinin produced a substantial stimulation of label found in PA, with an EC50 value of about 1 nM. This bradykinin stimulation of [32P]PA formation was only partially dependent on extracellular calcium, in contrast to the smaller response to nicotine, which was completely dependent on extracellular calcium. Short (10 min) pretreatment with tetradecanoylphorbol acetate (TPA) almost completely eliminated the bradykinin-stimulated formation of inositol phosphates, but failed to affect bradykinin stimulation of label in PA, suggesting that PA production in response to bradykinin is not downstream of phospholipase C activation. TPA alone failed to stimulate [32P]PA substantially, whereas long-term (24 or 48 h) treatment with TPA failed to attenuate the response to bradykinin. Diacylglycerol kinase inhibitors were also without effect on the bradykinin stimulation of [32P]PA. These results suggest that bradykinin stimulates PA production by a mechanism independent of the activation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator.

Science.gov (United States)

Ong, Cheung-Ter; Wong, Yi-Sin; Wu, Chi-Shun; Su, Yu-Hsiang

2017-01-01

Intravenous recombinant tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg body weight is associated with a high hemorrhagic transformation (HT) rate. Low-dose tPA (0.6 mg/kg) may have a lower hemorrhage rate but the mortality and disability rates at 90 days cannot be confirmed as non-inferior to standard-dose tPA. Whether the doses 0.7 and 0.8 mg/kg have better efficacy and safety needs further investigation. Therefore, this study is to compare the efficacy and safety of each dose of tPA (0.6, 0.7, 0.8, and 0.9 mg/kg body weight) and to investigate the factors affecting early neurological improvement (ENI) and early neurological deterioration (END). For this observational study, data were obtained from 274 patients who received tPA thrombolytic therapy in Chia-Yi Christian Hospital stroke unit. The tPA dose was given at the discretion of each physician. The definition of ENI was a >8 point improvement (compared with baseline) at 24 h following thrombolytic therapy or an improvement in the National Institutes of Health Stroke Score (NIHSS) to 0 or 1 toward the end of tPA infusion. The definition of END was a >4 point increase in NIHSS (compared with baseline) within 24 h of tPA infusion. The primary objective was to investigate whether 0.7 and 0.8 mg/kg of tPA have higher ENI rate, lower END rate, and better outcome at 6 months. Poor outcome was defined as having a modified Rankin Scale of 3 to 6 (range, 0 [no symptoms] to 6 [death]). The secondary objective was to investigate whether low-dose tPA has a lower risk of intracerebral HT than that with standard-dose tPA. We also investigated the factors affecting ENI, END, HT, and 6-month outcome. A total of 274 patients were included during the study period, of whom 260 were followed up for >6 months. There was a trend for the HT rate to increase as the dose increased ( P =0.02). The symptomatic HT rate was not significantly different among the low-dose and standard-dose groups. The ENI and END ( P =0.52) were

Effects of a tumor promoter and an anti-promoter on spontaneous and UV-induced 6-thioguanine-resistant mutations and sister-chromatid exchanges in V79 Chinese hamster cells

International Nuclear Information System (INIS)

Fujiwara, Y.; Kano, Y.; Tatsumi, M.; Paul, P.

1980-01-01

The effects of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or an anti-promoter antipain (protease inhibitor) on spontaneous and ultraviolet-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6TGsup(r)) recessive mutations were examined in V79 Chinese hamster cells in culture. TPA and/or antipain neither significantly altered base-line and UV-induced immediate SCE frequencies, nor decreased the level of delayed SCEs which persisted 6-7 days after irradiation. TPA and/or antipain appeared to enhance the recovery of UV-induced 6TGsup(r) colonies at the plateau expression phase despite non-mutagenicity by themselves and unaltered metabolic cooperation. Thus, the results conceivably imply that the 6TGsup(r)-recessive mutation expression, but not fixation, can be modulated at the cell level by TPA and/or antipain. Our results, together with the recent results of Loveday and Latt, may argue against the notion that TPA enhances the antipain-suppressible SCEs as an index of mitotic recombination in relevance with a tumor-promotion mechanism. (orig.)

Thrombin-specific inactivation of endothelial cell derived plasminogen activator

Energy Technology Data Exchange (ETDEWEB)

Highsmith, R.F.; Gallaher, M.J.

1986-03-05

Although thrombin (T) has diverse functions in the overall hemostatic mechanism, relatively little is known about its direct effect on components of the fibrinolytic enzyme system. The authors have investigated the interaction of T with plasminogen activators (PA) derived from bovine aortic endothelial cells (EC) in culture (2-5th passage, preconfluent monolayers). Varying concentrations of purified bovine or human thrombin were added to EC-conditioned media (CM). CM + T mixtures were assayed at various times for PA activity using purified plasminogen and a sensitive /sup 125/I-fibrinogenolytic or caseinolytic assay. T (5 nM), but not plasmin or trypsin at equivalent concentrations, resulted in a time-dependent inhibition of the PA activity in CM. T had no effect on the PA activity of urokinase, streptokinase or preformed plasmin. The ability of T to inactivate the EC-derived PA was abolished by prior treatment of T with active site-directed reagents. SDS-PAGE and zymography with copolymerized fibrinogen and plasminogen revealed further specificity in that only one of the multiple-molecular weight forms of PA present in EC-CM was inactivated by T. The authors conclude that in a highly specific fashion, T inactivates the predominant PA present in EC-CM by limited proteolysis. Thus, another potentially important function of T is suggested which may have particular significance in the temporal regulation of coagulation and fibrinolysis at the blood-endothelium interface.

Theory of even-parity states and two-photon spectra of conjugated polymers

Science.gov (United States)

McWilliams, P. C. M.; Hayden, G. W.; Soos, Z. G.

1991-04-01

The two-photon absorption (TPA) spectrum of interacting π electrons in conjugated polymers is shown to be qualitatively different from any single-particle description, including the Hartree-Fock limit. Alternating transfer integrals t(1+/-δ) along the backbone lead to a weak TPA below the one-photon gap Eg for arbitrarily weak correlations at δ=0, for intermediate correlations at δ=0.07 in polyenes, and for strong correlations at any δtheory to Eg in the limit of strong correlations in Hubbard models and is around 1.5Eg for Pariser-Parr-Pople (PPP) parameters. The PPP model, which accounts for one- and two-photon excitations of finite polyenes, is extended to even-parity states in polydiacetylenes (PDA's), polyacetylene (PA), and polysilanes (PS's). Previous experimental data for PDA and PS support both the strong TPA above Eg and weak TPA slightly below Eg for δ=0.15 in PDA and above Eg for δ~0.3 in PS. The strong TPA expected around 1.5Eg in isolated PA strands shifts to ~Eg due to interchain π-electron dispersion forces. TPA intensities in correlated states are shown to reflect both ionicity and mean-square charge separation. The even-parity states of conjugated polymers, like those of polyenes, show qualitatively different features associated with electron-electron correlations.

Fibrin-specific and effective clot lysis requires both plasminogen activators and for them to be in a sequential rather than simultaneous combination.

Science.gov (United States)

Pannell, R; Li, S; Gurewich, V

2017-08-01

Thrombolysis with tissue plasminogen activator (tPA) has been a disappointment and has now been replaced by an endovascular procedure whenever possible. Nevertheless, thrombolysis remains the only means by which circulation in a thrombosed artery can be restored rapidly. In contrast to tPA monotherapy, endogenous fibrinolysis uses both tPA and urokinase plasminogen activator (uPA), whose native form is a proenzyme, prouPA. This combination is remarkably effective as evidenced by the fibrin degradation product, D-dimer, which is invariably present in plasma. The two activators have complementary mechanisms of plasminogen activation and are synergistic in combination. Since tPA initiates fibrinolysis when released from the vessel wall and prouPA is in the blood, they induce fibrinolysis sequentially. It was postulated that this may be more effective and fibrin-specific. The hypothesis was tested in a model of clot lysis in plasma in which a clot was first exposed to tPA for 5 min, washed and incubated with prouPA. Lysis was compared with that of clots incubated with both activators simultaneously. The sequential combination was almost twice as effective and caused less fibrinogenolysis than the simultaneous combination (p < 0.0001) despite having significantly less tPA, as a result of the wash. A mechanism is described by which this phenomenon can be explained. The findings are believed to have significant therapeutic implications.

Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

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Kristine von Maltzan

2016-02-01

Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

Electro-optical and charge injection investigations of the donor-π-acceptor triphenylamine, oligocene–thiophene–pyrimidine and cyanoacetic acid based multifunctional dyes

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Ahmad Irfan

2015-10-01

Full Text Available The corner stone of present study is to tune the electro-optical and charge transport properties of donor-bridge-acceptor (D-π-A triphenylamine (TPA derivatives. In the present investigation, an electron deficient moiety (pyrimidine, electron-rich moiety (thiophene and oligocene (benzene, naphthalene, anthracene, tetracene and pentacene have been incorporated as π-spacer between the donor TPA unit and cyanoacetic acid acceptor and anchoring group. The elongation of bridge usually affects the energy levels, i.e., higher the highest occupied molecular orbital (HOMO while lower the lowest unoccupied molecular orbital (LUMO thus reduces the HOMO–LUMO energy gap. The lowered LUMO energy levels of cyano-{2-[6-(4-diphenylamino-phenyl-pyrimidin-4-yl]-tetraceno[2,3-b]thiophen-8-yl}-acetic acid (TPA-PTT4 and cyano-{2-[6-(4-diphenylamino-phenyl-pyrimidin-4-yl]-pentaceno[2,3-b]thiophen-9-yl}-acetic acid (TPA-PPT5 dyes revealed that electron injected from dye to semiconductor surface might be auxiliary stable resulting in impediment of quenching. The broken co-planarity between the π-spacer conceiving LUMO and the TPA moiety would help to impede the recombination process. Moreover, it is expected that TPA derivatives with the tetracenothiophene and pentacenothiophene moieties as π-bridge would show better photovoltaic performance due to lowered LUMO energy level, higher electronic coupling constant, light harvesting efficiency and electron injection values.

50Hz Extremely Low Frequency Electromagnetic Fields Enhance Protein Carbonyl Groups Content in Cancer Cells: Effects on Proteasomal Systems

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A. M. Eleuteri

2009-01-01

Full Text Available Electromagnetic fields are an assessed cause of prolonging free radicals lifespan. This study was carried out to investigate the influence of extremely low frequency electromagnetic fields on protein oxidation and on the 20S proteasome functionality, the complex responsible for the degradation of oxidized proteins. Caco 2 cells were exposed, for 24–72 hours, to 1 mT, 50 Hz electromagnetic fields. The treatment induced a time-dependent increase both in cell growth and in protein oxidation, more evident in the presence of TPA, while no changes in cell viability were detected. Exposing the cells to 50 Hz electromagnetic fields caused a global activation of the 20S proteasome catalytic components, particularly evident at 72 hours exposure and in the presence of TPA. The finding that EGCG, a natural antioxidant compound, counteracted the field-related pro-oxidant effects demonstrates that the increased proteasome activity was due to an enhancement in intracellular free radicals.

Polarized two-photon photoselection in EGFP: Theory and experiment.

Science.gov (United States)

Masters, T A; Marsh, R J; Blacker, T S; Armoogum, D A; Larijani, B; Bain, A J

2018-04-07

In this work, we present a complete theoretical description of the excited state order created by two-photon photoselection from an isotropic ground state; this encompasses both the conventionally measured quadrupolar (K = 2) and the "hidden" degree of hexadecapolar (K = 4) transition dipole alignment, their dependence on the two-photon transition tensor and emission transition dipole moment orientation. Linearly and circularly polarized two-photon absorption (TPA) and time-resolved single- and two-photon fluorescence anisotropy measurements are used to determine the structure of the transition tensor in the deprotonated form of enhanced green fluorescent protein. For excitation wavelengths between 800 nm and 900 nm, TPA is best described by a single element, almost completely diagonal, two-dimensional (planar) transition tensor whose principal axis is collinear to that of the single-photon S 0 → S 1 transition moment. These observations are in accordance with assignments of the near-infrared two-photon absorption band in fluorescent proteins to a vibronically enhanced S 0 → S 1 transition.

A benchmark report on MVA Berlin, the key element of waste management in Berlin; MVA Berlin als Herzstueck der Berliner Entsorgung im Vergleich mit der Wettbewerbs-Benchmark

Energy Technology Data Exchange (ETDEWEB)

Kempin, T. [Berliner Stadtreinigungsbetrieb, Berlin (Germany)

2004-07-01

The MVA Ruhleben incinerator has state-of-the-art technology, volume-dependent prime costs of 100-130 EUR/t, an acceptance payment of 63.70 EUR/t, employees covered by collective agreement system, disposal capacities of 500,000 tpa of residues, ecological sustainability, and customer-friendliness. Its importance will increase in the future as more than half of the expected waste volume of 983,000 tpa will be processed from 2005. (orig.) [German] Die MVA Ruhleben gewaehrleistet derzeit den Stand der Technik, mengenabhaengige Selbstkosten zwischen 100 EUR/t und 130 EUR/t, ein Annahmeentgelt von 63,70 EUR/t, soziale tarifgebundene Arbeitsplaetze, Entsorgungssicherheit, derzeit fuer 500.000 Tonnen Abfall pro Jahr, oekologische Nachhaltigkeit, Kundenfreundlichkeit. Die MVA Ruhleben wird zukuenftig fuer die Abfallentsorgung in Berlin eine noch groessere Bedeutung haben. Mit etwa 520.000 t/a Abfallentsorgungskapazitaet wird sie mehr als die Haelfte des erwarteten ueberlassungspflichtigen Restabfallaufkommens von 983.000 t/a ab 2005 verarbeiten. (orig.)

Polarized two-photon photoselection in EGFP: Theory and experiment

Science.gov (United States)

Masters, T. A.; Marsh, R. J.; Blacker, T. S.; Armoogum, D. A.; Larijani, B.; Bain, A. J.

2018-04-01

In this work, we present a complete theoretical description of the excited state order created by two-photon photoselection from an isotropic ground state; this encompasses both the conventionally measured quadrupolar (K = 2) and the "hidden" degree of hexadecapolar (K = 4) transition dipole alignment, their dependence on the two-photon transition tensor and emission transition dipole moment orientation. Linearly and circularly polarized two-photon absorption (TPA) and time-resolved single- and two-photon fluorescence anisotropy measurements are used to determine the structure of the transition tensor in the deprotonated form of enhanced green fluorescent protein. For excitation wavelengths between 800 nm and 900 nm, TPA is best described by a single element, almost completely diagonal, two-dimensional (planar) transition tensor whose principal axis is collinear to that of the single-photon S0 → S1 transition moment. These observations are in accordance with assignments of the near-infrared two-photon absorption band in fluorescent proteins to a vibronically enhanced S0 → S1 transition.

Enhanced Size Selection in Two-Photon Excitation for CsPbBr3 Perovskite Nanocrystals.

Science.gov (United States)

Chen, Junsheng; Chábera, Pavel; Pascher, Torbjörn; Messing, Maria E; Schaller, Richard; Canton, Sophie; Zheng, Kaibo; Pullerits, Tõnu

2017-10-19

Cesium lead bromide (CsPbBr 3 ) perovskite nanocrystals (NCs), with large two-photon absorption (TPA) cross-section and bright photoluminescence (PL), have been demonstrated as stable two-photon-pumped lasing medium. With two-photon excitation, red-shifted PL spectrum and increased PL lifetime is observed compared with one-photon excitation. We have investigated the origin of such difference using time-resolved laser spectroscopies. We ascribe the difference to the enhanced size selection of NCs by two-photon excitation. Because of inherent nonlinearity, the size dependence of absorption cross-section under TPA is stronger. Consequently, larger size NCs are preferably excited, leading to longer excited-state lifetime and red-shifted PL emission. In a broad view, the enhanced size selection in two-photon excitation of CsPbBr 3 NCs is likely a general feature of the perovskite NCs and can be tuned via NC size distribution to influence their performance within NC-based nonlinear optical materials and devices.

Efficacy of transpalatal arch as an anchorage reinforcing unit during orthodontic space closure: A three-dimensional finite element study

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Vishal Shrishail Kudagi

2017-01-01

Full Text Available Background and Objectives: Connecting the contralateral upper molars by means of a transpalatal arch (TPA is thought to decrease the tendency of the molars to move mesially in response to orthodontic force (i.e., provide orthodontic anchorage. This study was hence conducted to investigate the effects of the TPA on the displacement of the molars and stresses generated in the periodontium during orthodontic tooth movement using the finite element method (FEM. Materials and Methods: A three-dimensional (3D model was generated using medical modeling software (Mimics using the computed tomography slice images of the skull which were obtained at a slice thickness of 1 mm. From this, the finite element model was built using HyperMesh and analysis was performed using PATRAN software (MSC Software Corporation, 4675 MacArthur Court, Newport Beach, California 92660. The 3D finite element models were fabricated in two versions such as maxillary first molars including their associated periodontal ligament and alveolar bone one with TPA and another without TPA. Both were subjected to orthodontic forces, and the resultant stress patterns and displacements between the models with and without TPA were determined. Results: The stress and displacement plots in this study failed to show any significant differences in stress and displacement within the periodontium of molars, between the two models – one with TPA and the other without, in response to the orthodontic force. Interpretation and Conclusion: The results of the current finite element analysis, therefore, suggest that the presence of a TPA brings about no change in the initial dental and periodontal stress distribution and displacement.

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.

Protein kinase Cepsilon is important for migration of neuroblastoma cells

International Nuclear Information System (INIS)

Stensman, Helena; Larsson, Christer

2008-01-01

Migration is important for the metastatic capacity and thus for the malignancy of cancer cells. There is limited knowledge on regulatory factors that promote the migration of neuroblastoma cells. This study investigates the hypothesis that protein kinase C (PKC) isoforms regulate neuroblastoma cell motility. PKC isoforms were downregulated with siRNA or modulated with activators and inhibitors. Migration was analyzed with scratch and transwell assays. Protein phosphorylation and expression levels were measured with Western blot. Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced migration of SK-N-BE(2)C neuroblastoma cells. Treatment with the general protein kinase C (PKC) inhibitor GF109203X and the inhibitor of classical isoforms Gö6976 inhibited migration while an inhibitor of PKCβ isoforms did not have an effect. Downregulation of PKCε, but not of PKCα or PKCδ, with siRNA led to a suppression of both basal and TPA-stimulated migration. Experiments using PD98059 and LY294002, inhibitors of the Erk and phosphatidylinositol 3-kinase (PI3K) pathways, respectively, showed that PI3K is not necessary for TPA-induced migration. The Erk pathway might be involved in TPA-induced migration but not in migration driven by PKCε. TPA induced phosphorylation of the PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS) which was suppressed by the PKC inhibitors. Treatment with siRNA oligonucleotides against different PKC isoforms before stimulation with TPA did not influence the phosphorylation of MARCKS. PKCε is important for migration of SK-N-BE(2)C neuroblastoma cells. Neither the Erk pathway nor MARCKS are critical downstream targets of PKCε but they may be involved in TPA-mediated migration

ANALISIS DAMPAK PENGGEMBALAAN SAPI DI TPA (Studi Kasus di TPA Piyungan – Yogjakarta

OpenAIRE

Wahyono, Sri

2016-01-01

The end of municipal solid waste operations is landfill. Almost all of the Indonesia city’s landfills use the open dumping system. Generally, wastes dumped in the landfill are dominated by organic materials that potentially used for cow feeding. So that, in some landfills there are cow pasturing with the low cost operation related to the free feeding materials. According to UU No 18/2008, in the year of 2013 open dumping landfill is prohibited operate changed by sanitary landfill. Related to ...

Analisis Dampak Penggembalaan Sapi Di Tpa (Studi Kasus Di Tpa Piyungan – Yogjakarta

OpenAIRE

Wahyono, Sri

2010-01-01

The end of municipal solid waste operations is landfill. Almost all of the Indonesia city's landfills use the open dumping system. Generally, wastes dumped in the landfill are dominated by organic materials that potentially used for cow feeding. So that, in some landfills there are cow pasturing with the low cost operation related to the free feeding materials. According to UU No 18/2008, in the year of 2013 open dumping landfill is prohibited operate changed by sanitary landfill. Related to ...

Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L.

Science.gov (United States)

Nishino, H; Hayashi, T; Arisawa, M; Satomi, Y; Iwashima, A

1993-01-01

Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA-enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid.

Development of a glucose oxidase-based biocatalyst adopting both physical entrapment and crosslinking, and its use in biofuel cells

Science.gov (United States)

Chung, Yongjin; Ahn, Yeonjoo; Christwardana, Marcelinus; Kim, Hansung; Kwon, Yongchai

2016-04-01

New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high electron transfer rate, followed by excellent catalytic activity and EBC performance.New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high

MODEL DINAMIS PENGELOLAAN SAMPAH UNTUK MENGURANGI BEBAN PENUMPUKAN

Directory of Open Access Journals (Sweden)

Isti Surjandari

2009-01-01

Full Text Available The high volume of waste generated by both industry and society is a common problem found in almost all cities, especially in big cities like Jakarta. It is influenced by purchasing power and level of population growth. This problem become more worst with the limited landfill (TPA which are available. Therefore, it is required for an alternative waste management that can reduce waste level in TPA. The objective of this study is to analyze waste management that can reduce the waste level in TPA using simulation based on dynamic system. Simulation results will then be used to look at the feasibility of each alternative waste management based on Cost-Benefit ratio (B/C, whereas to determine the public's perception of alternative waste treatment (in terms of social, economic, environmental and technological aspects, a weighting process will be done using the Analytic Hierarchy Process (AHP. TPA Bantar Gebang which serves to accommodate waste generated by Jakarta was chosen as case study. Using simulation, projection of waste disposed to TPA Bantar Gebang for different scenarios to the year 2025 were obtained. Based on the dynamic simulation, AHP, and B/ C analysis, the study shows that the waste management should be done in two stages, first is by composting and then with incenerator. Abstract in Bahasa Indonesia: Tingginya volume sampah yang dihasilkan baik oleh industri maupun masyarakat merupakan permasalahan umum yang dijumpai di hampir semua kota, terutama di kota-kota besar seperti Jakarta. Disamping dipengaruhi oleh daya beli masyarakat, permasalahan tingginya volume sampah juga dipengaruhi oleh tingkat pertumbuhan penduduk. Permasalahan ini semakin dipersulit dengan terbatasnya Tempat Pembuangan Akhir (TPA yang tersedia. Untuk itu diperlukan suatu alternatif pengelolaan sampah yang dapat menurunkan tingkat penumpukan sampah di TPA. Dalam penelitian ini dilakukan analisis pengelolaan sampah untuk mengurangi beban penumpukan sampah di TPA

The analysis of waste treatment methods and managerial skills towards the effectiveness of CO2 emmissions (an ex post facto study at TPA Bantar Gebang Bekasi)

Science.gov (United States)

Ria Rajagukguk, Jenni; Siagian, Lestina

2017-09-01

In the last three years, Java Island produces 29.413.336 m3/year of waste, coming from settlement (house hold) and non-settlement waste. Recently, this waste is managed with conventional technology, composting and recycling. Based on law No. 18 of 2008 on Waste Management, Chapter III Article 5, it is firmly stated that the government and regional governments are responsible for ensuring proper and environmentally sound waste management in accordance with the objectives. The observation of managerial skills is highly needed to investigate the operation of waste management at TPA Bantar Gebang towards the effectiveness of CO2 emissions.The problems are (1)Whether there is any influence between the method of waste management through Biogas Technology to the effectiveness of CO2 emissions. (2) Whether there is any influence between managerial skills to effectiveness of CO2 emission. (3) Whether there is any simultaneous influence between waste management method and managerial skill to CO2 emission effectiveness and (4) how is the method of waste management. Quantitative and egineering method were used to process the data.Biogas Technology variables and Managerial Skill are simultaneously and significantly influenced to CO2 Emission Effectiveness, this is based on Fh > Ft value of 168,453 > 3.072467) and its significance is 0.000 accepted which means that variable of Managerial Skill have influence or very big influence to Effeciveness of CO2 Emission, Correlation coefficient value 94,1% which means there is very strong relation between variable of Biogas Technology, Managerial Skill to Effectiveness of CO2 emission. Then Technology management through Biogas Technology is anaerobic biology.

Perfil cognitivo y psicopatológico asociados a la conducta antisocial

OpenAIRE

John Jairo Cifuentes González; Nora Helena Londoño Arredondo

2011-01-01

El objetivo del presente estudio fue establecer los componentes del perfil cognitivo y psicopatológico que caracterizan a los individuos judicialmente condenados, discriminando además el diagnóstico de trastorno de la personalidad antisocial (TPA). Participaron 607 personas que se dividieron en dos grupos: 398 casos (con TPA) y 209 controles (sin TPA). Instrumentos: YSQ-L (Young y Brown, 1999) validado por Castrillón et al. (2005), EEC-M (Londoño et al., 2006), el MCMI-II (Millon, 1999) y la ...

Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

Science.gov (United States)

Tellier, Liane E; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J; Guldberg, Robert E; Temenoff, Johnna S

2018-05-01

As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.

1H NMR structural characterization of a recombinant kringle 2 domain from human tissue-type plasminogen activator

International Nuclear Information System (INIS)

Byeon, I.J.L.; Llinas, M.; Kelley, R.F.

1989-01-01

The kringle 2 domain of human tissue-type plasminogen activator (t-PA) has been characterized via 1 H NMR spectroscopy at 300 and 620 MHz. The experiments were performed on the isolated domain obtained by expression of the 174-263 portion of t-PA in Escherichia coli. The spectrum of t-Pa kringle 2 is characteristic of a globular structure and shows overall similarity to that of the plasminogen (PGN) kringle 4. Spectral comparison with human and bovine PGN kringle 4 identified side-chain resonances from Leu 46 , which afford a fingerprint of kringle folding, and from most of the aromatic ring spin systems. Ligand-binding studies confirm that t-PA kringle 2 binds L-lysine with an association constant K a ∼ 11.9 mM -1 . The data indicate that homologous or conserved residues relative to those that compose the lysine-binding sites of PGN kringles 1 and 4 are involved in the binding of L-lysine to t-PA kringle 2. These include Tyr 36 and, within the kringle inner loop, Trp 62 , His 64 , Trp 72 , and Tyr 74 . Several labile NH protons of t-PA kringle 2 exhibit retarded H-exchange kinetics, requiring more than a week in 2 H 2 O for full deuteration in the presence of L-lysine at 37 degree C. This reveals that kringle 2 is endowed with a compact, dynamically stable conformation. Proton Overhauser experiments in 1 H 2 O, centered on well-resolved NH resonances between 9.8 and 12 ppm, identify signals arising from the His 48a imidazole NH3 proton and the three Trp indole NH1 protons. Overall, the data indicate a highly structured conformation for the recombinant t-PA kringle 2 that is closely related to that of the previously investigated PGN kringles 1, 4, and 5

TEMPAT PENITIPAN ANAK, MEWAH, MENENGAH DAN SEDERHANA (Studi Perbandingan Perkembangan Anak Balita Secara Kognitif Motorik Afektif

Directory of Open Access Journals (Sweden)

Listia Natadjaja

2007-01-01

Full Text Available The aim of this study is to observe the comparison of children cognitive, motorist and affective development in luxurious, middle and moderate day care center,, in order to obtain the description of a suitable day care center and its influence. All the population which is known and registered in Social Department are used, like: Teratai, Sandhy Putra, LKK, Dharma Wanita Day Care Center and also many private day care center like: Benih Kasih, St Yoseph and RKZ. The purposive sampling method is used to show that the aim of this technique is to reach the specific target. The examination result shows that there are differences in children development among the different day care center for cognitive and motorizes development, but only in certain ages. The Architectural element in luxurious, middle and moderate day care center is suspected to give effects in children development. Abstract in Bahasa Indonesia : Penelitian ini meneliti perbandingan perkembangan kognitif, motorik dan afektif anak balita di tempat penitipan anak yang tergolong mewah, menengah dan sederhana,sehingga didapatkan gambaran tempat penitipan anak yang sesuai dan bagaimanakah pengaruhnya. Penelitian ini menggunakan populasi sebagai obyek penelitian yang diketahui dan terdaftar di dinas sosial yaitu: TPA. Teratai, TPA. Sandhy Putra, TPA. LKK, TPA. Dharma Wanita, dan tempat penitipan swasta lainnya, yaitu: TPA. Benih Kasih, TPA. St. Yoseph, TPA. RKZ. Metode proposive sampling dipakai sebagai acuan yang menunjukkan bahwa teknik ini digunakan untuk mencapai tujuan-tujuan tertentu. Hasil penelitian ini menyatakan bahwa terdapat perbedaan perkembangan anak pada tempat penitipan anak yang berbeda untuk perkembangan kognitif dan motorik, namun tidak merata pada semua kelompok usia.Elemen arsitektur yang berbeda pada kategori mewah, menengah dan sederhana diduga berpengaruh pada tingkat perkembangan anak. Kata kunci: tempat penitipan anak, perkembangan anak, elemen arsitektur.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

Science.gov (United States)

James, Brandon; Chang, Andrew D; McTaggart, Ryan A; Hemendinger, Morgan; Mac Grory, Brian; Cutting, Shawna M; Burton, Tina M; Reznik, Michael E; Thompson, Bradford; Wendell, Linda; Mahta, Ali; Siket, Matthew; Madsen, Tracy E; Sheth, Kevin N; Nouh, Amre; Furie, Karen L; Jayaraman, Mahesh V; Khatri, Pooja; Yaghi, Shadi

2018-02-27

Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction.

Science.gov (United States)

Goyal, Akash; Yu, Francois T H; Tenwalde, Mathea G; Chen, Xucai; Althouse, Andrew; Villanueva, Flordeliza S; Pacella, John J

2017-07-01

We have previously reported that long-tone-burst, high-mechanical-index ultrasound (US) and microbubble (MB) therapy can restore perfusion in both in vitro and in vivo models of microvascular obstruction (MVO). Addition of MBs to US has been found to potentiate the efficacy of thrombolytics on large venous thrombi; however, the optimal US parameters for achieving microvascular reperfusion of MVO caused by microthrombi, when combined with tissue plasminogen activator (tPA), are unknown. We sought to elucidate the specific effects of US, with and without tPA, for effective reperfusion of MVO in an in vitro model using both venous and arterial microthrombi. Venous- and arterial-type microthrombi were infused onto a mesh with 40-μm pores to simulate MVO. Pulsed US (1 MHz) was delivered with inertial cavitation (IC) (1.0 MPa, 1000 cycles, 0.33 Hz) and stable cavitation (SC) US (0.23 MPa, 20% duty cycle, 0.33 Hz) regimes while MB suspension (2 × 10 6  MBs/mL) was infused. The efficacy of sonoreperfusion with these parameters was tested with and without tPA. Sonoreperfusion efficacy was significantly greater for IC + tPA compared with tPA alone, IC, SC and SC + tPA, suggesting lytic synergism between tPA and US for both venous- and arterial-type microthrombi. In contrast to our previous in vitro studies using 1.5 MPa at 5000 US cycles without tPA, the IC regime employed herein used 90% less US energy. These findings suggest an IC regime can be used with tPA synergistically to achieve a high degree of fibrinolysis for both thrombus types. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Hyperglycemia, Acute Ischemic Stroke and Thrombolytic Therapy

Science.gov (United States)

Bruno, Askiel; Fagan, Susan C.; Ergul, Adviye

2014-01-01

Ischemic stroke is a leading cause of disability and is considered now the 4th leading cause of death. Many clinical trials have shown that stroke patients with acute elevation in blood glucose at onset of stroke suffer worse functional outcomes, longer in-hospital stay and higher mortality rates. The only therapeutic hope for these patients is the rapid restoration of blood flow to the ischemic tissue through intravenous administration of the only currently proven effective therapy, tissue plasminogen activator (tPA). However, even this option is associated with the increased risk of intracerebral hemorrhage. Nonetheless, the underlying mechanisms through which hyperglycemia (HG) and tPA worsen the neurovascular injury after stroke are not fully understood. Accordingly, this review summarizes the latest updates and recommendations about the management of HG and co-administration of tPA in a clinical setting while focusing more on the various experimental models studying: 1. the effect of HG on stroke outcomes; 2. the potential mechanisms involved in worsening the neurovasular injury; 3. the different therapeutic strategies employed to ameliorate the injury, and finally; 4. the interaction between HG and tPA. Developing therapeutic strategies to reduce the hemorrhage risk with tPA in hyperglycemic setting is of great clinical importance. This can best be achieved by conducting robust preclinical studies evaluating the interaction between tPA and other therapeutics in order to develop potential therapeutic strategies with high translational impact. PMID:24619488

Effect of stifle angle on the magnitude of the tibial plateau angle measurement in dogs with intact and transected cranial cruciate ligament. A cadaveric study.

Science.gov (United States)

Aulakh, K S; Harper, T A M; Lanz, O I; Daniel, G B; Werre, S R

2011-01-01

To determine the effect of stifle angle on the magnitude of the radiographic tibial plateau angle (TPA) in normal and cranial cruciate ligament (CCL) -deficient stifles. Three pairs of canine cadaver hindlimbs from three skeletally mature dogs were positioned in a custom-made positioning device. A lateral radiograph of each specimen was obtained before and after transection of the CCL at four stifle angles (90°, 110°, 135° and 140-150° [i.e. maximum extension]), based on goniometric measurements. Four observers determined the radiographic TPA twice for each radiograph with a minimum of two days between each measurement. The radiographic TPA measurements in all specimens at different stifle angles with intact CCL and transected CCL were compared with mixed-model ANOVA. The effect of stifle angle, CCL transection, and interaction between the two on observer TPA measurement variability was also determined using the coefficient of variation. Tibial plateau angle was not statistically different in the stifle angles for either the intact or transected CCL. There was also no statistical difference for TPA between intact and transected CCL groups at each of the stifle angles. Stifle angle, CCL transection and interaction between the two did not have any significant effect for intra-observer and inter-observer variation. The angle of the stifle during radiography does not influence the magnitude of the TPA measurement as determined on true lateral radiographs of the stifle and tibia in cadaveric canine limbs.

Influences of alcoholic solvents on spray pyrolysis deposition of TiO{sub 2} blocking layer films for solid-state dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Jiang, Changyun, E-mail: jiangc@imre.a-star.edu.sg [Institute of Materials Research and Engineering, A-STAR, 3 Research Link, 117602 Singapore (Singapore); Koh, Wei Lin; Leung, Man Yin [Institute of Materials Research and Engineering, A-STAR, 3 Research Link, 117602 Singapore (Singapore); Hong, Wei [Department of Chemical Engineering and Waterloo Institute for Nanotechnology (WIN), University of Waterloo, 200 University Ave West ON, Waterloo, Canada N2L 3G1 (Canada); Li, Yuning, E-mail: yuning.li@uwaterloo.ca [Institute of Materials Research and Engineering, A-STAR, 3 Research Link, 117602 Singapore (Singapore); Department of Chemical Engineering and Waterloo Institute for Nanotechnology (WIN), University of Waterloo, 200 University Ave West ON, Waterloo, Canada N2L 3G1 (Canada); Zhang, Jie [Institute of Materials Research and Engineering, A-STAR, 3 Research Link, 117602 Singapore (Singapore)

2013-02-15

Influences of alcoholic solvents for titanium diisopropoxide bis(acetylacetonate) (TPA) precursor solutions on the spray pyrolysis deposited TiO{sub 2} films and the photovoltaic performance of the solid-state dye-sensitized solar cells (SDSCs) using these TiO{sub 2} films as the blocking layers were investigated. Smooth TiO{sub 2} films were obtained by spray pyrolysis deposition of a TPA solution in isopropanol (IPA) at a relatively low temperature of 260 Degree-Sign C. On the other hand, when ethanol was used as solvent, the TiO{sub 2} films fabricated at the same temperature showed much rougher surfaces with many pinholes. Our results showed that ethanol reacts with TPA to form titanium diethoxide bis(acetylacetonate) (TEA), which requires a higher thermal decomposition temperature than that of TPA. SDSCs with TiO{sub 2} blocking layer films fabricated using a TPA solution in IPA showed higher power conversion efficiencies with smaller variations. - Graphical abstract: Alcoholic solvents used for the TiO{sub 2} precursor play a critical role in determining the surface morphology of blocking layers and thus the photovoltaic performance of the SDSCs. Highlights: Black-Right-Pointing-Pointer Solvent influences morphology of spray pyrolysis deposited TiO{sub 2} blocking layer. Black-Right-Pointing-Pointer Ethanol reacts with TPA, resulting poor quality of blocking layer. Black-Right-Pointing-Pointer Isopropanol is better than ethanol for obtaining smooth blocking layer. Black-Right-Pointing-Pointer SDSC with blocking layer made with isopropanol showed better performance.

Electroabsorption in triphenylamine-based hole-transporting materials for organic light-emitting diodes

International Nuclear Information System (INIS)

Stampor, Waldemar; Mroz, Wojciech

2007-01-01

Electric-field modulated absorption (EA) spectra have been studied in solid films of triphenylamine (TPA)-based compounds, commonly used as hole-transporting materials in organic light-emitting diodes. The electroabsorption spectra of triphenyldiamine derivatives (TPD and TAPC) and a starburst amine dendrimer m-MTDATA are compared with those of TPA which is the building block of the molecules. The EA results indicate that properties of excited states of m-MTDATA and TAPC can be qualitatively rationalized in the terms of exciton interaction between TPA constituents. The lowest energy electronic excitations of m-MTDATA dendrimer are strongly delocalized within the area of the whole molecule. In contrast to m-MTDATA and TAPC, the TPD behavior in the electric field shows individual features that can not be derived from the optical properties of TPA monomers alone. The influence of excited state degeneracy on EA spectra is discussed. The consistent qualitative interpretation of EA spectra for compounds under investigation has been reached assuming that the second derivative lineshapes of EA signal originate from degenerate (in TPA and m-MTDATA) and possible quasi-degenerate states (in TAPC and TPD)

Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

International Nuclear Information System (INIS)

Kido, H.; Fukusen, N.; Katunuma, N.

1987-01-01

In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4β-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17β-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells

Efficacy of 'Tailored Physical Activity' on reducing sickness absence among health care workers: A 3-months randomised controlled trial.

Science.gov (United States)

Andersen, Lotte Nygaard; Juul-Kristensen, Birgit; Roessler, Kirsten Kaya; Herborg, Lene Gram; Sørensen, Thomas Lund; Søgaard, Karen

2015-10-01

The aim was to evaluate efficacy of "Tailored Physical Activity" (TPA) versus a reference group (REF) in reducing the number of self-reported days of sickness absence for health care workers in the Sonderborg Municipality. In this randomised controlled trial, all participants (n = 54) received health guidance for 1.5 h and were randomised to TPA or REF. The primary aim was to make a comparison of participants' self-reported sickness absence due to musculoskeletal troubles measured three months after baseline. Secondary outcomes included anthropometric, health-related and physical capacity measures. A TPA intervention was not significantly more effective than REF in reducing sickness absence caused by musculoskeletal troubles. However, there were significant improvements for TPA participants compared to REF in reducing pain intensity from 47.9 mm to 21.8 mm (p health care workers since participants achieved a substantial effect on their experience of pain, on their work ability and on their fear of physical movement relating to pain. Moreover, a difference in aerobic capacity was apparent between the sample groups. TPA however, had no significant effect in reducing sickness absence days. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential retinoic acid inhibition of ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate and by germicidal ultraviolet light

International Nuclear Information System (INIS)

Lichti, U.; Patterson, E.; Hennings, H.; Yuspa, S.H.

1981-01-01

Several retinoids including retinoic acid effectively inhibit phorbol ester-mediated tumor promotion and ornithine decarboxylase (ODC) induction in mouse epidermis. To understand better the possible cellular site of action of retinoids, the inhibitory action of retinoic acid on the induction of ODC was compared for two distinctly different inducers, namely, 12-O-tetradecanoylphorbol-13-acetate (TPA) and germicidal ultraviolet light (uv), in primary mouse epidermal cell cultures. It was found that the induction of ODC by TPA is almost completely prevented by retinoic acid while the induction by uv is only moderately inhibited. The differential inhibition of enzyme induction cannot be accounted for by selective retinoid inhibition of DNA, RNA, or protein synthesis either alone or in concert with TPA or uv. These agents possibly act at transcription or translation, both of which are required for ODC induction by TPA or uv

Conjugated donor-acceptor-acceptor (D-A-A) molecule for organic nonvolatile resistor memory.

Science.gov (United States)

Dong, Lei; Li, Guangwu; Yu, An-Dih; Bo, Zhishan; Liu, Cheng-Liang; Chen, Wen-Chang

2014-12-01

A new donor-acceptor-acceptor (D-A-A) type of conjugated molecule, N-(4-(N',N'-diphenyl)phenylamine)-4-(4'-(2,2-dicyanovinyl)phenyl) naphthalene-1,8-dicarboxylic monoimide (TPA-NI-DCN), consisting of triphenylamine (TPA) donors and naphthalimide (NI)/dicyanovinylene (DCN) acceptors was synthesized and characterized. In conjunction with previously reported D-A based materials, the additional DCN moiety attached as end group in the D-A-A configuration can result in a stable charge transfer (CT) and charge-separated state to maintain the ON state current. The vacuum-deposited TPA-NI-DCN device fabricated as an active memory layer was demonstrated to exhibit write-once-read-many (WORM) switching characteristics of organic nonvolatile memory due to the strong polarity of the TPA-NI-DCN moiety. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitive measurement of nonlinear absorption and optical limiting in undoped and Fe-doped ZnO quantum dots using pulsed laser

Science.gov (United States)

Sharma, D.; Malik, B. P.; Gaur, A.

2016-11-01

Zinc oxide quantum dots (QDs) with Fe-doping at different concentrations were prepared by chemical co-precipitation method. The prepared QDs were characterized by UV-Vis spectroscopy, X-ray diffraction and Z-scan technique. The sizes of QDs were found to be within 4.6-6.6 nm range. The nonlinear parameters viz. two-photon absorption coefficient (βTPA) and two-photon absorption cross-section (σTPA) were extracted with the help of open aperture Z-scan technique using nanosecond Nd:YAG laser operating at wavelength 532 nm. Higher values of βTPA and σTPA for Fe doped ZnO implied that they were potential materials for development of photonics devices and sensor protection applications. Fe doped sample (3 % by wt) was found to be the best optical limiter with limiting threshold intensity of 0.64 TW/cm2.

Identification and characterization of Taenia solium enolase as a plasminogen-binding protein.

Science.gov (United States)

Ayón-Núñez, Dolores A; Fragoso, Gladis; Espitia, Clara; García-Varela, Martín; Soberón, Xavier; Rosas, Gabriela; Laclette, Juan P; Bobes, Raúl J

2018-06-01

The larval stage of Taenia solium (cysticerci) is the causal agent of human and swine cysticercosis. When ingested by the host, T. solium eggs are activated and hatch in the intestine, releasing oncospheres that migrate to various tissues and evolve into cysticerci. Plasminogen (Plg) receptor proteins have been reported to play a role in migration processes for several pathogens. This work is aimed to identify Plg-binding proteins in T. solium cysticerci and determine whether T. solium recombinant enolase (rTsEnoA) is capable of specifically binding and activating human Plg. To identify Plg-binding proteins, a 2D-SDS-PAGE ligand blotting was performed, and recognized spots were identified by MS/MS. Seven proteins from T. solium cysticerci were found capable of binding Plg: fascicilin-1, fasciclin-2, enolase, MAPK, annexin, actin, and cytosolic malate dehydrogenase. To determine whether rTsEnoA binds human Plg, a ligand blotting was performed and the results were confirmed by ELISA both in the presence and absence of εACA, a competitive Plg inhibitor. Finally, rTsEnoA-bound Plg was activated to plasmin in the presence of tPA. To better understand the evolution of enolase isoforms in T. solium, a phylogenetic inference analysis including 75 enolase amino acid sequences was conducted. The origin of flatworm enolase isoforms, except for Eno4, is independent of their vertebrate counterparts. Therefore, herein we propose to designate tapeworm protein isoforms as A, B, C, and 4. In conclusion, recombinant enolase showed a strong plasminogen binding and activating activity in vitro. T. solium enolase could play a role in parasite invasion along with other plasminogen-binding proteins. Copyright © 2018 Elsevier B.V. All rights reserved.

Estudo dos m?todos de extra??o e comportamento do f?sforo na Terra Preta Arqueol?gica da mesorregi?o central do estado do Amazonas

OpenAIRE

Pessoa Junior, Erasmo S?rgio Ferreira

2016-01-01

As Terras Pretas Arqueol?gicas (TPA) s?o os Antrossolos conhecidos por serem os solos mais f?rteis da Amaz?nia. Uma das caracter?sticas das TPA ? a presen?a de fragmentos cer?micos arqueol?gicos, bem como alta quantidade de f?sforo e c?lcio. Esses fatos s?o usados como um registro importante da ocupa??o da Amaz?nia por civiliza??es pr?-colombianas. Este trabalho apresenta resultados sobre os m?todos de extra??o do f?sforo em TPA de oito s?tios da Mesorregi?o Central do Estado d...

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)...

Effects of electron-withdrawing group and electron-donating core combinations on physical properties and photovoltaic performance in D-pi-A star-shaped small molecules

NARCIS (Netherlands)

Luponosov, Yuriy N.; Min, Jie; Solodukhin, Alexander N.; Kozlov, Oleg V.; Obrezkova, Marina A.; Peregudova, Svetlana M.; Ameri, Tayebeh; Chvalun, Sergei N.; Pshenichnikov, Maxim S.; Brabec, Christoph J.; Ponomarenko, Sergei A.

The first representatives of star-shaped molecules having 3-alkylrhodanine (alkyl-Rh) electron-withdrawing groups, linked through bithiophene pi-spacer with electron-donating either triphenylamine (TPA) or tris(2-methoxyphenyl)amine (m-TPA) core were synthesized. The physical properties and

Phosphorescence spectroscopy and its application to the study of colloidal dynamics

NARCIS (Netherlands)

Lettinga, M.P.

1999-01-01

The technique of Time-resolved phosphorescence anisotropy (TPA) has been frequently used to study rotational motions of particles on the micro- to millisecond time-scale. The interpretation of the observed TPA signals is, however, not straightforward. The theoretical description of the

Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary clot retention in an in vitro model.

Science.gov (United States)

Ritch, Chad R; Ordonez, Maria A; Okhunov, Zhamshid; Araujo, Juan; Walsh, Rhonda; Baudin, Vania; Lee, Daniel; Badani, Ketan K; Gupta, Mantu; Landman, Jaime

2009-08-01

The management of urinary clot retention and hematuria involves manual irrigation with sterile water or normal saline via a Foley catheter followed by continuous bladder irrigation. Irrigation may become difficult because of the formation of dense blood clots. Tissue plasminogen activator (t-PA/Alteplase) may be a useful pharmacological agent to improve the efficacy of manual irrigation of large, dense clots. The goal of the current study was to compare t-PA to sterile water for clot irrigation in an in vitro model. In vitro models of clot retention were created using 500-cc urinary leg bags each filled with 80 cc of unpreserved whole blood from a healthy volunteer. Each model was incubated at 25 degrees C for 24 hours to allow clot formation. Four models each with 25 mL solution of t-PA at concentrations of 2, 1, 0.5, and 0.25 mg/mL were evaluated and compared to a control (25 mL sterile water). Models were instilled with solution (t-PA or control) and incubated for 30 minutes at 37 degrees C, and then irrigated with sterile water via 18F Foley by a blinded investigator. Three separate experiments were conducted, and statistical analysis was performed comparing various irrigation parameters. Clot evacuation with 25 mL of t-PA at a concentration of 2 mg/mL (50 mg) was significantly easier (p = 0.05) and faster (p < 0.05) than the sterile water control. The mean time for clot evacuation in this model was 2.7 minutes for t-PA solution 2 mg/mL versus 7.3 minutes for the control (p < 0.05). Compared to the control, irrigation with t-PA solution 2 mg/mL also required less irrigant (180 mL vs. 500 mL) (p < 0.05) for complete evacuation. There was a similar trend in efficacy for the lower doses of t-PA, but this was not statistically significant. In this in vitro study, a single 25 mL instillation of t-PA solution 2 mg/mL is significantly better than sterile water alone for clot evacuation. In vivo animal studies are pending.

Peripheral Hole Acceptor Moieties on an Organic Dye Improve Dye‐Sensitized Solar Cell Performance

Science.gov (United States)

Hao, Yan; Gabrielsson, Erik; Lohse, Peter William; Yang, Wenxing; Johansson, Erik M. J.; Hagfeldt, Anders

2015-01-01

Investigation of charge transfer dynamics in dye‐sensitized solar cells is of fundamental interest and the control of these dynamics is a key factor for developing more efficient solar cell devices. One possibility for attenuating losses through recombination between injected electrons and oxidized dye molecules is to move the positive charge further away from the metal oxide surface. For this purpose, a metal‐free dye named E6 is developed, in which the chromophore core is tethered to two external triphenylamine (TPA) units. After photoinduced electron injection into TiO2, the remaining hole is rapidly transferred to a peripheral TPA unit. Electron–hole recombination is slowed down by 30% compared to a reference dye without peripheral TPA units. Furthermore, it is found that the added TPA moieties improve the electron blocking effect of the dye, retarding recombination of electrons from TiO2 to the cobalt‐based electrolyte. PMID:27722076

Construction and expression of a recombinant antibody-targeted plasminogen activator

International Nuclear Information System (INIS)

Schnee, J.M.; Runge, M.S.; Matsueda, G.A.; Hudson, N.W.; Seidman, J.G.; Haber, E.; Quertermous, T.

1987-01-01

Covalent linkage of tissue-type plasminogen activator (t-PA) to a monoclonal antibody specific for the fibrin β chain (anti-fibrin 59D8) results in a thrombolytic agent that is more specific and more potent that t-PA alone. To provide a ready source of this hybrid molecule and to allow tailoring of the active moieties for optimal activity, the authors have engineered a recombinant version of the 59D8-t-PA conjugate. The rearranged 59D8 heavy chain gene was cloned and combined in the expression vector pSV2gpt with sequence coding for a portion of the γ2b constant region and the catalytic β chain of t-PA. This construct was transfected into heavy chain loss variant cells derived form the 59D8 hybridoma. Recombinant protein was purified by affinity chromatography and analyzed with electrophoretic transfer blots and radioimmunoassay. These revealed a 65-kDa heavy chain-t-PA fusion protein that is secreted in association with the 59D8 light chain in the form of a 170-kDa disulfide-linked dimer. Chromogenic substrate assays showed the fusion protein to have 70% of the peptidolytic activity of native t-PA and to activate plasminogen as efficiently as t-PA. IN a competitive binding assay, reconstituted antibody was shown to have a binding profile similar to that of native 59D8. Thus, by recombinant techniques, they have produced a hybrid protein capable of high affinity fibrin binding and plasminogen activation

Hierarchical coassembly of DNA–triptycene hybrid molecular building blocks and zinc protoporphyrin IX

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Rina Kumari

2016-05-01

Full Text Available Herein, we describe the successful construction of composite DNA nanostructures by the self-assembly of complementary symmetrical 2,6,14-triptycenetripropiolic acid (TPA–DNA building blocks and zinc protoporphyrin IX (Zn PpIX. DNA–organic molecule scaffolds for the composite DNA nanostructure were constructed through covalent conjugation of TPA with 5′-C12-amine-terminated modified single strand DNA (ssDNA and its complementary strand. The repeated covalent conjugation of TPA with DNA was confirmed by using denaturing polyacrylamide gel electrophoresis (PAGE, reverse-phase high-performance liquid chromatography (RP-HPLC and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF. The biologically relevant photosensitizer Zn PpIX was used to direct the hybridization-mediated self-assembly of DNA–TPA molecular building blocks as well as a model guest molecule within the DNA–TPA supramolecular self-assembly. The formation of fiber-like composite DNA nanostructures was observed. Native PAGE, circular dichroism (CD and atomic force microscopy (AFM have been utilized for analyzing the formation of DNA nanofibers after the coassembly. Computational methods were applied to discern the theoretical dimension of the DNA–TPA molecular building block of the nanofibers. A notable change in photocatalytic efficiency of Zn PpIX was observed when it was inside the TPA–DNA scaffold. The significant increase in ROS generation by Zn PpIX when trapped in this biocompatible DNA–TPA hybrid nanofiber may be an effective tool to explore photodynamic therapy (PDT applications as well as photocatalytic reactions.

Inflammation, oxidative DNA damage, and carcinogenesis

International Nuclear Information System (INIS)

Lewis, J.G.; Adams, D.O.

1987-01-01

Inflammation has long been associated with carcinogenesis, especially in the promotion phase. The mechanism of action of the potent inflammatory agent and skin promoter 12-tetradecanoyl phorbol-13-acetate (TPA) is unknown. It is though that TPA selectively enhances the growth of initiated cells, and during this process, initiated cells progress to the preneoplastic state and eventually to the malignant phenotype. The authors and others have proposed that TPA may work, in part, by inciting inflammation and stimulating inflammatory cells to release powerful oxidants which then induce DNA damage in epidermal cells. Macrophages cocultured with target cells and TPA induce oxidized thymine bases in the target cells. This process is inhibited by both catalase and inhibitors of lipoxygenases, suggesting the involvement of both H 2 O 2 and oxidized lipid products. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin that C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H 2 O 2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice. These data support the hypothesis that inflammation and the release of genotoxic oxidants may be one mechanism whereby initiated cells receive further genetic insults. They also further complicate risk assessment by suggesting that some environmental agents may work indirectly by subverting host systems to induce damage rather than maintaining homeostasis

Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

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Yuqian Li

2017-08-01

Full Text Available Spontaneous intracerebral hemorrhage (ICH is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA or tissue-type plasminogen activator (tPA has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45 or tPA (tPA group, n = 41, respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

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2013-03-27

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Continuous Sound Velocity Measurements along the Shock Hugoniot Curve of Quartz

Science.gov (United States)

Li, Mu; Zhang, Shuai; Zhang, Hongping; Zhang, Gongmu; Wang, Feng; Zhao, Jianheng; Sun, Chengwei; Jeanloz, Raymond

2018-05-01

We report continuous measurements of the sound velocity along the principal Hugoniot curve of α quartz between 0.25 and 1.45 TPa, as determined from lateral release waves intersecting the shock front as a function of time in decaying-shock experiments. The measured sound velocities are lower than predicted by prior models, based on the properties of stishovite at densities below ˜7 g /cm3 , but agree with density functional theory molecular dynamics calculations and an empirical wide-regime equation of state presented here. The Grüneisen parameter calculated from the sound velocity decreases from γ ˜1 .3 at 0.25 TPa to 0.66 at 1.45 TPa. In combination with evidence for increased (configurational) specific heat and decreased bulk modulus, the values of γ suggest a high thermal expansion coefficient at ˜0. 25 - 0 .65 TPa , where SiO2 is thought to be a bonded liquid. From our measurements, dissociation of the molecular bonds persists to ˜0. 65 - 1 .0 TPa , consistent with estimates by other methods. At higher densities, the sound velocity is close to predictions from previous models, and the Grüneisen parameter approaches the ideal gas value.

CpG Oligonucleotide and Interleukin 2 stimulation enables higher cytogenetic abnormality detection rates than 12-o-tetradecanolyphorbol-13-acetate in Asian patients with B-cell chronic lymphocytic leukemia (B-CLL).

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Liaw, Fiona Pui San; Lau, Lai Ching; Lim, Alvin Soon Tiong; Lim, Tse Hui; Lee, Geok Yee; Tien, Sim Leng

2014-12-01

The present study was designed to compare abnormality detection rates using DSP30 + IL2 and 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Asian patients with B-CLL. Hematological specimens from 47 patients (29 newly diagnosed, 18 relapsed) were established as 72 h-DSP30 + IL2 and TPA cultures. Standard methods were employed to identify clonal aberrations by conventional cytogenetics (CC). The B-CLL fluorescence in situ hybridization (FISH) panel comprised ATM, CEP12, D13S25, and TP53 probes. DSP30 + IL2 cultures had a higher chromosomal abnormality detection rate (67 %) compared to TPA (44 %, p 0.05). Thirteen cases with abnormalities were found exclusively in DSP30 + IL2 cultures compared to one found solely in TPA cultures. DSP30 + IL2 cultures were comparable to the FISH panel in detecting 11q-, +12 and 17p- but not 13q-. It also has a predilection for 11q- bearing leukemic cells compared to TPA. FISH had a higher abnormality detection rate (84.1 %) compared to CC (66.0 %) with borderline significance (p = 0.051), albeit limited by its coverage. In conclusion, DSP30 + IL2 showed a higher abnormality detection rate. However, FISH is indispensable to circumvent low mitotic indices and detect subtle abnormalities.

Staphylococcus aureus manganese transport protein C (MntC is an extracellular matrix- and plasminogen-binding protein.

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Natália Salazar

Full Text Available Infections caused by Staphylococcus aureus--particularly nosocomial infections--represent a great concern. Usually, the early stage of pathogenesis consists on asymptomatic nasopharynx colonization, which could result in dissemination to other mucosal niches or invasion of sterile sites, such as blood. This pathogenic route depends on scavenging of nutrients as well as binding to and disrupting extracellular matrix (ECM. Manganese transport protein C (MntC, a conserved manganese-binding protein, takes part in this infectious scenario as an ion-scavenging factor and surprisingly as an ECM and coagulation cascade binding protein, as revealed in this work. This study showed a marked ability of MntC to bind to several ECM and coagulation cascade components, including laminin, collagen type IV, cellular and plasma fibronectin, plasminogen and fibrinogen by ELISA. The MntC binding to plasminogen appears to be related to the presence of surface-exposed lysines, since previous incubation with an analogue of lysine residue, ε-aminocaproic acid, or increasing ionic strength affected the interaction between MntC and plasminogen. MntC-bound plasminogen was converted to active plasmin in the presence of urokinase plasminogen activator (uPA. The newly released plasmin, in turn, acted in the cleavage of the α and β chains of fibrinogen. In conclusion, we describe a novel function for MntC that may help staphylococcal mucosal colonization and establishment of invasive disease, through the interaction with ECM and coagulation cascade host proteins. These data suggest that this potential virulence factor could be an adequate candidate to compose an anti-staphylococcal human vaccine formulation.

Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

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Lacroix, Romaric; Plawinski, Laurent; Robert, Stéphane; Doeuvre, Loïc; Sabatier, Florence; Martinez de Lizarrondo, Sara; Mezzapesa, Anna; Anfosso, Francine; Leroyer, Aurelie S.; Poullin, Pascale; Jourde, Noémie; Njock, Makon-Sébastien; Boulanger, Chantal M.; Anglés-Cano, Eduardo; Dignat-George, Françoise

2012-01-01

Background We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and Methods Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. Results Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. Conclusions Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium. PMID:22733025

Browse Title Index

African Journals Online (AJOL)

Items 3801 - 3850 of 11090 ... Vol 8, No 15 (2009), Effect of plasmin and heparin on in vitro ... simplex optimization medium (KSOM) and embryo screening ... Vol 14, No 13 (2015), Effect of recombinant bovine somatotropin application intervals ...

Longer term follow-up on effects of Tailored Physical Activity or Chronic Pain Self-Management Programme on return-to-work

DEFF Research Database (Denmark)

Andersen, Lotte Nygaard; Juul-Kristensen, Birgit; Sørensen, Thomas Lund

2016-01-01

the reference group as regards return-to-work. Compared with the reference group no other benefits of TPA and CPSMP were evident regarding pain, work ability, kinesiophobia or physical capacity. CONCLUSION: After 11 months TPA, the reference group, and CPSMP show similar patterns of facilitating return...

Temporal pole signal abnormality on MR imaging in temporal lobe epilepsy with hippocampal sclerosis: a fluid-attenuated inversion-recovery study.

Science.gov (United States)

Carrete, Henrique; Abdala, Nitamar; Lin, Kátia; Caboclo, Luís Otávio; Centeno, Ricardo Silva; Sakamoto, Américo Ceiki; Szjenfeld, Jacob; Nogueira, Roberto Gomes; Yacubian, Elza Márcia Targas

2007-09-01

To determine the frequency and regional involvement of temporal pole signal abnormality (TPA) in patients with hippocampal sclerosis (HS) using fluid-attenuated inversion-recovery (FLAIR) MR imaging, and to correlate this feature with history. Coronal FLAIR images of the temporal pole were assessed in 120 patients with HS and in 30 normal subjects, to evaluate gray-white matter demarcation. Ninety (75%) of 120 patients had associated TPA. The HS side made difference regarding the presence of TPA, with a left side prevalence (p=0.04, chi2 test). The anteromedial zone of temporal pole was affected in 27 (30%) out of 90 patients. In 63 (70%) patients the lateral zone were also affected. Patients with TPA were younger at seizure onset (p=0.018), but without association with duration of epilepsy. Our FLAIR study show temporal pole signal abnormality in 3/4 of patients with HS, mainly seen on the anteromedial region, with a larger prevalence when the left hippocampus was involved.

Activity deprivation induces neuronal cell death: mediation by tissue-type plasminogen activator.

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Eldi Schonfeld-Dado

Full Text Available Spontaneous activity is an essential attribute of neuronal networks and plays a critical role in their development and maintenance. Upon blockade of activity with tetrodotoxin (TTX, neurons degenerate slowly and die in a manner resembling neurodegenerative diseases-induced neuronal cell death. The molecular cascade leading to this type of slow cell death is not entirely clear. Primary post-natal cortical neurons were exposed to TTX for up to two weeks, followed by molecular, biochemical and immunefluorescence analysis. The expression of the neuronal marker, neuron specific enolase (NSE, was down-regulated, as expected, but surprisingly, there was a concomitant and striking elevation in expression of tissue-type plasminogen activator (tPA. Immunofluorescence analysis indicated that tPA was highly elevated inside affected neurons. Transfection of an endogenous tPA inhibitor, plasminogen activator inhibitor-1 (PAI-1, protected the TTX-exposed neurons from dying. These results indicate that tPA is a pivotal player in slowly progressing activity deprivation-induced neurodegeneration.

Temporal pole signal abnormality on MR imaging in temporal lobe epilepsy with hippocampal sclerosis: a fluid-attenuated inversion-recovery study

International Nuclear Information System (INIS)

Carrete Junior, Henrique; Abdala, Nitamar; Szjenfeld, Jacob; Nogueira, Roberto Gomes; Lin, Katia; Caboclo, Luis Otavio; Centeno, Ricardo Silva; Sakamoto, Americo Ceiki; Yacubian, Elza Marcia Targas

2007-01-01

Objective: To determine the frequency and regional involvement of temporal pole signal abnormality (TPA) in patients with hippocampal sclerosis (HS) using fluid-attenuated inversion-recovery (FLAIR) MR imaging, and to correlate this feature with history. Method: Coronal FLAIR images of the temporal pole were assessed in 120 patients with HS and in 30 normal subjects, to evaluate gray-white matter demarcation. Results: Ninety (75%) of 120 patients had associated TPA. The HS side made difference regarding the presence of TPA, with a left side prevalence (p=0.04, χ 2 test). The anteromedial zone of temporal pole was affected in 27 (30%) out of 90 patients. In 63 (70%) patients the lateral zone were also affected. Patients with TPA were younger at seizure onset (p=0.018), but without association with duration of epilepsy. Conclusion: Our FLAIR study show temporal pole signal abnormality in 3/4 of patients with HS, mainly seen on the anteromedial region, with a larger prevalence when the left hippocampus was involved. (author)

Reducing Haemorrhagic Transformation after Thrombolysis for Stroke: A Strategy Utilising Minocycline

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David J. Blacker

2013-01-01

Full Text Available Haemorrhagic transformation (HT of recently ischaemic brain is a feared complication of thrombolytic therapy that may be caused or compounded by ischaemia-induced activation of matrix metalloproteinases (MMPs. The tetracycline antibiotic minocycline inhibits matrix MMPs and reduces macroscopic HT in rodents with stroke treated with tissue plasminogen activator (tPA. The West Australian Intravenous Minocycline and TPA Stroke Study (WAIMATSS aims to determine the safety and efficacy of adding minocycline to tPA in acute ischaemic stroke. The WAIMATSS is a multicentre, prospective, and randomised pilot study of intravenous minocycline, 200 mg 12 hourly for 5 doses, compared with standard care, in patients with ischaemic stroke treated with intravenous tPA. The primary endpoint is HT diagnosed by brain CT and MRI. Secondary endpoints include clinical outcome measures. Some illustrative cases from the early recruitment phase of this study will be presented, and future perspectives will be discussed.

REACH MUSC: A Telemedicine Facilitated Network for Stroke: Initial Operational Experience

Science.gov (United States)

Adams, Robert J.; Debenham, Ellen; Chalela, Julio; Chimowitz, Marc; Hays, Angela; Hill, Cody; Holmstedt, Christine; Jauch, Edward; Kitch, Alec; Lazaridis, Christos; Turan, Tanya N.

2012-01-01

REACH Medical University of South Carolina (MUSC) provides stroke consults via the internet in South Carolina. From May 2008 to April 2011 231 patients were treated with intravenous (IV) thrombolysis and 369 were transferred to MUSC including 42 for intra-arterial revascularization [with or without IV tissue plasminogen activator (tPA)]. Medical outcomes and hemorrhage rates, reported elsewhere, were good (Lazaridis et al., 2011). Here we report operational features of REACH MUSC which covers 15 sites with 2,482 beds and 471,875 Emergency Department (ED) visits per year. Eight Academic Faculty from MUSC worked with 165 different physicians and 325 different nurses in the conduct of 1085 consults. For the 231 who received tPA, time milestones (in minutes) were: Onset to Door: 62 (mean), 50 (median); Door to REACH Consult: 43 and 33, Consult Request to Consult Start: was 9 and 7, Consult Start to tPA Decision: 31 and 25; Decision to Infusion: 20 and 14, and total Door to Needle: 98 and 87. The comparable times for the 854 not receiving tPA were: Onset to Door: 140 and 75; Door to REACH Consult: 61 and 41; Consult Request to Consult Start: 9 and 7, Consult Start to tPA Decision: 27 and 23. While the consultants respond to consult requests in <10, there is a long delay between arrival and Consult request. Tracking of operations indicates if we target shortening Door to Call time and time from tPA decision to start of drug infusion we may be able to improve Door to Needle times to target of <60. The large number of individuals involved in the care of these patients, most of whom had no training in REACH usage, will require novel approaches to staff education in ED based operations where turnover is high. Despite these challenges, this robust system delivered tPA safely and in a high fraction of patients evaluated using the REACH MUSC system. PMID:22435064

REACH MUSC: A telemedicine facilitated network for urgent stroke: initial experience

Directory of Open Access Journals (Sweden)

Robert J. Adams

2012-03-01

Full Text Available REACH MUSC provides stroke consults via the internet in South Carolina. From May 2008 to April 2011 231 patients were treated with intravenous (IV thrombolysis and 369 were transferred to Medical University of South Carolina (MUSC including 42 for intra-arterial revascularization (with or without IV tPA. Medical outcomes and hemorrhage rates, reported elsewhere, were good (Lazaridis et al. 2011, in press. Here we report operational features of REACH MUSC which covers 15 sites with 2,482 beds and 471,875 Emergency Department (ED visits per year. Eight Academic Faculty from MUSC worked with 165 different physicians and 325 different nurses in the conduct of 1085 consults. For the 231 who received tissue plasminogen activator (tPA, time milestones were: Onset to Door: 62 min (mean, 50 (median; Door to REACH Consult: 43 and 33, Consult Request to Consult Start: was 9 and 7 minutes, Consult Start to tPA Decision: 31 and 25 minutes; Decision to Infusion: 20 and 14 minutes, and total Door to Needle: 98 and 87 minutes. The comparable times for the 854 not receiving tPA were: Onset to Door: 140 and 75 minutes; Door to REACH Consult: 61 and 41 minutes; Consult Request to Consult Start 9 and 7 minutes, Consult Start to tPA Decision 27 and 23 minutes. While the consultants respond to consult requests in < 10 minutes, there is a long delay between arrival and Consult request. Tracking of operations indicates if we target shortening Door to Call time and time from tPA decision to start of drug infusion we may be able to improve Door to Needle times to target of < 60 minutes. The large number of individuals involved in the care of these patients, most of whom had no training in REACH usage,will require novel approaches to staff education in ED based operations where turnover is high. Despite these challenges this robust system delivered tPA safely and in a high fraction of patients evaluated using the REACH MUSC system.

Protective effect of Ocimum sanctum on 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene and aflatoxin B1 induced skin tumorigenesis in mice

Energy Technology Data Exchange (ETDEWEB)

Rastogi, Shipra; Shukla, Yogeshwer; Paul, Bhola N; Chowdhuri, D Kar; Khanna, Subhash K [Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001 (India); Das, Mukul [Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001 (India)

2007-11-01

A study on the protective effect of alcoholic extract of the leaves of Ocimum sanctum on 3-mthylcholanthrene (MCA), 7,12-dimethylbenzanthracene (DMBA) and aflatoxin B{sub 1} (AFB{sub 1}) induced skin tumorigenesis in a mouse model has been investigated. The study involved pretreatment of mice with the leaf extract prior to either MCA application or tetradecanoyl phorbol acetate (TPA) treatment in a two-stage tumor protocol viz a viz, DMBA/TPA and AFB1/TPA. The results of the present study indicate that the pretreatment with alcoholic extract of the leaves of O. sanctum decreased the number of tumors in MCA, DMBA/TPA and AFB1/TPA treated mice. The skin tumor induced animals pretreated with alcoholic extract led to a decrease in the expression of cutaneous {gamma}-glutamyl transpeptidase (GGT) and glutathione-S-transferase-P (GST-P) protein. The histopathological examination of skin tumors treated with leaf extract showed increased infiltration of polymorphonuclear, mononuclear and lymphocytic cells, decreased ornithine decarboxylase activity with concomitant enhancement of interleukin-1{beta} (IL-1{beta}) and tumor necrosis factor-{alpha} (TNF-{alpha}) in the serum, implying the in vivo antiproliferative and immunomodulatory activity of leaf extract. The decrease in cutaneous phase I enzymes and elevation of phase II enzymes in response to topical application of leaf extract prior to MCA, AFB1, DMBA/TPA and AFB1/TPA treatment indicate the possibility of impairment in reactive metabolite(s) formation and thereby reducing skin carcinogenicity. Furthermore, pretreatment of leaf extract in the carcinogen induced animals resulted in elevation of glutathione levels and decrease in lipid peroxidation along with heat shock protein expression, indicating a scavenging or antioxidant potential of the extract during chemical carcinogenesis. Thus it can be concluded that leaf extract of O. sanctum provides protection against chemical carcinogenesis in one or more of the

Enhanced adsorptive and photocatalytic achievements in removal of methylene blue by incorporating tungstophosphoric acid-TiO2 into MCM-41

International Nuclear Information System (INIS)

Zanjanchi, M.A.; Golmojdeh, H.; Arvand, M.

2009-01-01

The use of titania-dispersed materials in photocatalytic processes has been proposed as an alternative to the conventional bare TiO 2 , in order to modify the surface area and activity of the catalyst. A homogeneously dispersed Keggin unit into TiO 2 was synthesized using tungstophosphoric acid (TPA) and titanium tetraisopropoxide. This compound was then loaded into MCM-41 by dispersing it in a suspension containing the mesoporous phase. Two other titanium-containing MCM-41 catalysts, Ti-MCM-41 and TiO 2 /MCM-41 were also prepared using isomorphous substitution synthesis method and impregnation method, respectively, for the sake of comparison. The prepared photocatalysts were characterized by X-ray diffraction (XRD), nitrogen physisorption (BET) and chemical analysis. The catalysts were used to study degradation of methylene blue (MB) in aqueous solution. XRD result shows a pure anatase crystalline phase for TPA-containing TiO 2 indicating that there is good molecular distribution of tungstophosphoric acid into TiO 2 structure. Supported TPA-TiO 2 into MCM-41 shows both TPA-TiO 2 and MCM-41 characteristic X-ray reflections in the high-angle and low-angle parts of the XRD patterns, respectively. The experimental results show that adsorption is a major constituent in the elimination of MB from the dye solutions by the TPA-containing materials. Exploitation of both adsorption and photocatalytic processes speeds up the removal of the dye using the TPA-TiO 2 -loaded MCM-41 photocatalyst. The elimination of MB is completed within 15 min for a 30 mg l -1 MB solution containing a catalyst dose of 100 mg/100 ml. The efficiencies of the other photocatalysts such as commercial TiO 2 , Ti-MCM-41, TiO 2 /MCM-41 and TPA-TiO 2 for adsorption and degradation of MB were also studied and compared with that of the prepared catalyst.

The effect of ultrasound on thromboembolic model of brain stroke in rat

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Shabanzadeh A

2007-08-01

Full Text Available Background: Ultrasound (US has been used in neuroprotection after cerebral ischemia; however, its use is controversial. Application of US in combination with fibrinolytic agents may improve fibrinolytic effects. In this study the effects of US, alone or in combination with tissue plasminogen activator (tPA, on brain ischemic injury were examined and we studied whether US is protective in the brain injured by ischemia under normothermic conditions. Methods: We performed two studies. In the first study, rectal and brain temperatures were compared. In the second study, we studied whether US alone or in combination with tPA is neuroprotective in thromboembolic stroke. To induce focal cerebral ischemia, a clot was formed in a catheter. Once the clot had formed, the catheter was advanced 17 mm in the internal carotid artery until its tip was 1-2 mm away from the origin of the middle cerebral artery (MCA. The preformed clot in the catheter was then injected, and the catheter was removed. The wound was then closed and the infarction volume, edema and neurological deficits were measured after MCA occlusion. Results: The temperature in the brain was approximately 0.50 ºC lower than the rectal temperature. In the control, US+low tPA, low tPA, US+high tPA and, high tPA groups, the infarct volume (% was 34.56±4.16, 17.09±6.72, 21.25±7.8, 13.5±10.72 and 20.61±6.17 (mean ±SD at 48 h after MCA occlusion, respectively. The results indicate that US alone reduces the infarct volume by 30% compared to that of the control group (P<0.05. US improved neurological deficits and reduced brain edema significantly (p<0.05. Conclusions: This study indicate that US appears to have a protective effect, alone and in combination with tPA, in an embolic model of stroke.

Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

Science.gov (United States)

Gao, Fang; Wang, Guangya; Xu, Jinxiu

2017-01-01

Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mLtreatment, a significant decrease in FIB, PAI-1 and t-PA levels and an increase in APTT and DDI were observed in the severe SH group. In conclusion, SH patients displayed a distinct pattern of alteration of hemostatic parameters that was dependent on the severity of the disease. Patients with TSH levels ≥10 μIU/mL displayed hypercoagulability, which was reversed by 6 months of L-T4 treatment. © 2017 by the Association of Clinical Scientists, Inc.

Development of the optical sensor for discriminating isomers of fatty acids based on emissive network polymers composed of polyhedral oligomeric silsesquioxane.

Science.gov (United States)

Narikiyo, Hayato; Kakuta, Takahiro; Matsuyama, Hiroki; Gon, Masayuki; Tanaka, Kazuo; Chujo, Yoshiki

2017-07-01

It was shown that water-soluble network polymers composed of polyhedral oligomeric silsesquioxane (POSS) had hydrophobic spaces inside the network because of strong hydrophobicity of the cubic silica cage. In this study, the water-soluble POSS network polymers connected with triphenylamine derivatives (TPA-POSS) were synthesized, and their functions as a sensor for discriminating the geometric isomers of fatty acids were investigated. Accordingly, in the photoluminescence spectra, different time-courses of intensity and peak wavelengths of the emission bands were detected from the TPA-POSS-containing solution in the presence of cis- or trans-fatty acids during incubation. Furthermore, variable time-dependent changes were obtained by changing coexisting ratios between two geometric isomers. From the mechanistic investigation, it was implied that these changes could be originated from the difference in the degree of interaction between the POSS networks and each fatty acid. Our data could be applicable for constructing a sensing material for generation and proportion of trans-fatty acids in the oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis of metal-organic framework films by pore diffusion method

Science.gov (United States)

Murayama, Naohiro; Nishimura, Yuki; Kajiro, Hiroshi; Kishida, Satoru; Kinoshita, Kentaro; Tottori Univ Team; Nippon Steel; Sumitomo Metal Co. Collaboration; Tottori Integrated Frontier Resaerch Center (Tifrec) Collaboration; Tottori University Electronic Display Resaerch Center (Tedrec) Collaboration

Metal-organic frameworks (MOFs) presents high controllability in designing the nano-scale pore, and this enable molecular storages, catalysts, gas sensors, gas separation membranes, and electronic devices for next-generation. Therefore, a simple method for film synthesis of MOFs compared with conventional methods [1] is strongly required. In this paper, we provide pore diffusion method, in which a substrate containing constituent metals of MOF is inserted in solution that includes only linker molecules of MOF. As a result, 2D growth of MOF was effectively enhanced, and the formation of flat and dense MOF films was attained. The growth time, t, dependence of film thickness, d, can be expressed by the relation of d = Aln(t + 1) + B, where A and B are constants. It means that ionized coppers diffuse through the pores of MOFs and the synthesis reaction proceeds at the MOF/solvent interface. We demonstrated the fabrication of a HKUST-1/Cu-TPA hetero structure by synthesizing a Cu-TPA film continuously after the growth of a HKUST-1 film on the CuOx substrate.

A Retrospective Study on Genetic Heterogeneity within Treponema Strains: Subpopulations Are Genetically Distinct in a Limited Number of Positions.

Directory of Open Access Journals (Sweden)

Darina Čejková

Full Text Available Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA strains (Nichols, DAL-1, Mexico A, SS14, 4 T. p. ssp. pertenue (TPE strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc, 1 T. p. ssp. endemicum (TEN strain (Bosnia A and one strain (Cuniculi A of Treponema paraluisleporidarum ecovar Cuniculus (TPLC were examined with respect to the presence of nucleotide intrastrain heterogeneous sites.The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5, DAL-1 (n = 4, and SS14 (n = 7, TPE strain Samoa D (n = 1, and TEN strain Bosnia A (n = 5. Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes (tprC, GI, I, K, in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY, in genes involved in cell structure (murC, translation (prfA, general and DNA metabolism (putative SAM dependent methyltransferase, topA, and in seven hypothetical genes.Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process.

A Retrospective Study on Genetic Heterogeneity within Treponema Strains: Subpopulations Are Genetically Distinct in a Limited Number of Positions.

Science.gov (United States)

Čejková, Darina; Strouhal, Michal; Norris, Steven J; Weinstock, George M; Šmajs, David

2015-01-01

Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14), 4 T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), 1 T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPLC) were examined with respect to the presence of nucleotide intrastrain heterogeneous sites. The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes) were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5), DAL-1 (n = 4), and SS14 (n = 7), TPE strain Samoa D (n = 1), and TEN strain Bosnia A (n = 5). Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes (tprC, GI, I, K), in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY), in genes involved in cell structure (murC), translation (prfA), general and DNA metabolism (putative SAM dependent methyltransferase, topA), and in seven hypothetical genes. Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process.

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

Entering new fields of simulation application - challenges faced in simulation modelling of stroke systems

NARCIS (Netherlands)

van der Zee, D.J.; Monks, T.; Lahr, Maarten; Luijckx, Gert Jan; Buskens, Erik; Anagnostou, Anastasia; Hoad, Katy; Kunc, Martin

2016-01-01

Stroke is a major cause of death and long-term disability world-wide. To improve functional outcome treatment with intravenous tissue plasminogen activator (tPA) is the most effective medical treatment for acute brain infarction within 4.5 hours after the onset of stroke symptoms. Unfortunately, tPA

Efficacy of Tailored Physical Activity or Chronic Pain Self-Management Programme on return to work for sick-listed citizens

DEFF Research Database (Denmark)

Andersen, Lotte Nygaard; Juul-Kristensen, Birgit; Sørensen, Thomas Lund

2015-01-01

. In contrast, no benefit of TPA and CPSMP was evident regarding work ability, kinesiophobia or physical capacity after 3 months of follow-up. CONCLUSIONS: The results suggest that TPA is a promising intervention to facilitate return to work and reduce pain among sick-listed citizens with pain related...

Macrophage migration inhibitory factor triggers chemotaxis of CD74+CXCR2+ NKT cells in chemically induced IFN-γ-mediated skin inflammation.

Science.gov (United States)

Hsieh, Chia-Yuan; Chen, Chia-Ling; Lin, Yee-Shin; Yeh, Trai-Ming; Tsai, Tsung-Ting; Hong, Ming-Yuan; Lin, Chiou-Feng

2014-10-01

IFN-γ mediates chemically induced skin inflammation; however, the mechanism by which IFN-γ-producing cells are recruited to the sites of inflammation remains undefined. Secretion of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, from damaged cells may promote immune cell recruitment. We hypothesized that MIF triggers an initial step in the chemotaxis of IFN-γ-producing cells in chemically induced skin inflammation. Using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears, MIF expression was examined, and its role in this process was investigated pharmacologically. The cell populations targeted by MIF, their receptor expression patterns, and the effects of MIF on cell migration were examined. TPA directly caused cytotoxicity accompanied by MIF release in mouse ear epidermal keratinocytes, as well as in human keratinocytic HaCaT cells. Treatment with the MIF antagonist (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester considerably attenuated TPA-induced ear swelling, leukocyte infiltration, epidermal cell proliferation, and dermal angiogenesis. Inhibition of MIF greatly diminished the dermal infiltration of IFN-γ(+) NKT cells, whereas the addition of exogenous TPA and MIF to NKT cells promoted their IFN-γ production and migration, respectively. MIF specifically triggered the chemotaxis of NKT cells via CD74 and CXCR2, and the resulting depletion of NKT cells abolished TPA-induced skin inflammation. In TPA-induced skin inflammation, MIF is released from damaged keratinocytes and then triggers the chemotaxis of CD74(+)CXCR2(+) NKT cells for IFN-γ production. Copyright © 2014 by The American Association of Immunologists, Inc.

Antibodies directed to drug epitopes to investigate the structure of drug-protein photoadducts. Recognition of a common photobound substructure in tiaprofenic acid/ketoprofen cross-photoreactivity.

Science.gov (United States)

Lahoz, A; Hernández, D; Miranda, M A; Pérez-Prieto, J; Morera, I M; Castell, J V

2001-11-01

Drug-induced photoallergy is an immune adverse reaction to the combined effect of drugs and light. From the mechanistic point of view, it first involves covalent binding of drug to protein resulting in the formation of a photoantigen. Hence, determination of the structures of drug-protein photoadducts is of great relevance to understand the molecular basis of photoallergy and cross-immunoreactivity among drugs. Looking for new strategies to investigate the covalent photobinding of drugs to proteins, we generated highly specific antibodies to drug chemical substructures. The availability of such antibodies has allowed us to discriminate between the different modes by which tiaprofenic acid (TPA), suprofen (SUP), and ketoprofen (KTP) photobind to proteins. The finding that the vast majority of the TPA photoadduct can be accounted for by means of antibody anti-benzoyl strongly supports the view that the drug binds preferentially via the thiophene ring, leaving the benzene ring more accessible. By contrast, selective recognition of SUP-protein photoadducts by antibody anti-thenoyl evidences a preferential coupling via the benzene ring leaving the thiophene moiety more distant from the protein matrix. In the case of KTP, photoadducts are exclusively recognized by antibody anti-benzoyl, indicating that the benzene ring is again more accessible. As a result of this research, we have been able to identify a common substructure that is present in TPA-albumin and KTP-albumin photoadducts. This is remarkable since, at a first sight, the greatest structural similarities can be found between TPA and SUP as they share the same benzoylthiophene chromophore. These findings can explain the previously reported observations of cross-reactivity to KTP (or TPA) in patients photosensitized to TPA (or KTP).

Effectiveness of time-related interventions in children with ADHD aged 9-15 years: a randomized controlled study.

Science.gov (United States)

Wennberg, Birgitta; Janeslätt, Gunnel; Kjellberg, Anette; Gustafsson, Per A

2018-03-01

Specific problems with time and timing that affect daily routines, homework, school work, and social relations have been recognized in children with ADHD. The primary treatments for children with ADHD do not specifically focus on time-related difficulties. The aim of this randomized controlled study (RCT) was to investigate how multimodal interventions, consisting of training in time-processing ability (TPA) and compensation with time-assistive devices (TAD), affect TPA and daily time management (DTM) in children with ADHD and time difficulties, compared with only educational intervention. Thirty-eight children on stable medication for ADHD in the 9-15-year age range were randomly allocated to an intervention or a control group. The children's TPA was measured with a structured assessment (KaTid), and the children's DTM was rated by a parent questionnaire (Time-Parent scale) and by children's self-reporting (Time-Self-rating). The intervention consisted of time-skill training and compensation with TAD. Data were analysed for differences in TPA and in DTM between the control and intervention groups in the 24-week follow-up. Children in the intervention group increased their TPA significantly (p = 0.019) more compared to the control group. The largest increase was in orientation to time. In addition, the parents in the intervention group rated their children's DTM as significantly (p = 0.01) improved compared with the parents in the control group. According to the children, their DTM was not significantly changed. In conclusion, a multimodal intervention consisting of time-skill training and TAD improved TPA and DTM in children with ADHD aged 9-15 years.

Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis

DEFF Research Database (Denmark)

Roldan, A.L.; Cubellis, M.V.; Masucci, M.T.

1990-01-01

, and therefore the capacity of cells to migrate and invade neighboring tissues. We have isolated a 1.4 kb cDNA clone coding for the entire human uPAR. An oligonucleotide synthesized on the basis of the N-terminal sequence of the purified protein was used to screen a cDNA library made from SV40 transformed human......, a size very close to that of the cloned cDNA. Expression of the uPAR cDNA in mouse cells confirms that the clone is complete and expresses a functional uPA binding protein, located on the cell surface and with properties similar to the human uPAR. Caseinolytic plaque assay, immunofluorescence analysis......The surface receptor for urokinase plasminogen activator (uPAR) has been recognized in recent years as a key molecule in regulating plasminogen mediated extracellular proteolysis. Surface plasminogen activation controls the connections between cells, basement membrane and extracellular matrix...

Structure-based engineering of species selectivity in the interaction between urokinase and its receptor: implication for preclinical cancer therapy

DEFF Research Database (Denmark)

Lin, Lin; Gårdsvoll, Henrik; Huai, Qing

2010-01-01

The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface-associated plasminogen activation. Because plasmin activity controls fibrinolysis in a variety of pathological conditions, including cancer...

Characterization of three novel adhesins of Leptospira interrogans.

Science.gov (United States)

Siqueira, Gabriela H; Atzingen, Marina V; Alves, Ivy J; de Morais, Zenaide M; Vasconcellos, Silvio A; Nascimento, Ana L T O

2013-12-01

We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In silico analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral surface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. Leptospira spp. may use these interactions as possible mechanisms during the establishment of infection.

Efficient near-infrared emission of π-extended cyclometalated iridium complexes based on pyrene in solution-processed polymer light-emitting diode

Science.gov (United States)

Liu, Yu; Hao, Zhaoran; Meng, Fanyuan; Wang, Pu; Yang, Liang; Wang, Yafei; Pei, Yong; Su, Shijian

2018-05-01

A novel iridium complex grafting hole-transporting triphenylamine (TPA) unit onto cyclometalated ligand, namely t-BuPyrPyTPA)2Ir(acac), was successfully synthesized and characterized. The photophysical, electrochemical and DFT/TD-DFT calculation, as well as electroluminescence properties of this iridium complex were fully investigated. Meanwhile, the PLEDs employing (t-BuPyrPyTPA)2Ir(acac) as dopant presented stable NIR emission peaked at 697 nm and a shoulder at 764 nm with a highest external quantum efficiency (EQE) of 0.56% at 4 wt% dopant concentration. These results demonstrate that expanding the conjugation length of the ligand is an effective way to achieve NIR emission.

Does intravenous administration of recombinant tissue plasminogen activator for ischemic stroke can cause inferior myocardial infarction?

Directory of Open Access Journals (Sweden)

Mostafa Almasi

2016-06-01

Full Text Available Recombinant tissue plasminogen activator (rTPA is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved.

Phantom studies of triple photon absorptiometry and bone mineral measurement at a hip prosthesis

International Nuclear Information System (INIS)

Farrell, T.J.; Webber, C.E.

1992-01-01

The feasibility of using triple photon absorptiometry (TPA) for the measurement of bone mineral mass about a hip prosthesis was examined. A theoretical expression describing the variance of TPA measurements was verified using a triple photon source and phantom materials which simulate the soft tissue-bone mineral-metal prosthesis system. The expression for the variance was used to determine an optimized set of photon energies. It was shown that a precision of 3% could be obtained for reasonable measurement times using this optimized set of energies and that TPA should be a feasible approach for measurement of bone mineral about a hip prosthesis. (orig.)

KLF10, transforming growth factor-{beta}-inducible early gene 1, acts as a tumor suppressor

Energy Technology Data Exchange (ETDEWEB)

Song, Ki-Duk [Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921 (Korea, Republic of); Laboratory of Protein Engineering and Comparative Immunology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-921 (Korea, Republic of); Kim, Duk-Jung [The Institute of Hankook Life Science, 7-9 Myungryun-dong, Jongno-gu, Seoul 110-521 (Korea, Republic of); Lee, Jong Eun [Department of Anatomy, College of Medicine, Yonsei University, Seoul 120-752 (Korea, Republic of); Yun, Cheol-Heui [Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921 (Korea, Republic of); Laboratory of Protein Engineering and Comparative Immunology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-921 (Korea, Republic of); Lee, Woon Kyu, E-mail: wklee@inha.ac.kr [Laboratory of Developmental Genetics, School of Medicine, Inha University, Incheon 400-712 (Korea, Republic of); Brain Korea 21 Center for Advanced Medical Education, School of Medicine, Inha University, Incheon 400-712 (Korea, Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer KLF10{sup -/-} mice exhibited accelerated papilloma development after DMBA/TPA treatment. Black-Right-Pointing-Pointer KLF10{sup -/-} keratinocytes showed increased proliferation and apoptosis. Black-Right-Pointing-Pointer KLF10{sup -/-} MEFs yielded more colonies than wild-type one with H-Ras transfection. Black-Right-Pointing-Pointer KLF10 dose-dependently activated p21{sup WAF1/CIP1} transcription. Black-Right-Pointing-Pointer KLF10 is a tumor suppressor and that it targets p21{sup WAF1/CIP1} transcription. -- Abstract: Krueppel-like factor 10 (KLF10) has been suggested to be a putative tumor suppressor. In the present study, we generated KLF10 deficient mice to explore this hypothesis in vivo. KLF10 deficient mice exhibited increased predisposition to skin tumorigenesis and markedly accelerated papilloma development after DMBA/TPA treatment. On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis. In colony formation assays after oncogenic H-Ras transfection, KLF10 deficient mouse embryonic fibroblasts (MEFs) yielded more colonies than wild-type MEFs. Furthermore, KLF10 dose-dependently activated p21{sup WAF1/CIP1} transcription, which was independent of p53 and Sp1 binding sites in p21{sup WAF1/CIP1} promoter. This study demonstrates that KLF10 is a tumor suppressor and that it targets p21{sup WAF1/CIP1} transcription.

Selective C--C coupling of ir-ethene and ir-carbenoid radicals

NARCIS (Netherlands)

Dzik, W.I.; Reek, J.N.H.; de Bruin, B.

2008-01-01

The reactivity of the paramagnetic iridium(II) complex [IrII(ethene)(Me3tpa)]2+ (1) (Me3tpa=N,N,N-tris(6-methyl-2-pyridylmethyl) amine) towards the diazo compounds ethyl diazoacetate (EDA) and trimethylsilyldiazomethane (TMSDM) was investigated. The reaction with EDA gave rise to selective CC bond

Influence of two-photon absorption on soliton self-frequency shift

DEFF Research Database (Denmark)

Steffensen, Henrik; Agger, Christian; Bang, Ole

2012-01-01

In this paper we develop an analytical model for the soliton self-frequency shift, which includes second- and thirdorder dispersion, self-steepening, the full Raman term, and, for the first time to our best knowledge, the effect of two-photon absorption (TPA). We show that TPA can have a signific...

Early Recanalization Postintravenous Thrombolysis in Ischemic Stroke with Large Vessel Occlusion: A Digital Subtraction Angiography Study.

Science.gov (United States)

Mao, Yi-Ting; Mitchell, Peter; Churilov, Leonid; Dowling, Richard; Dong, Qiang; Yan, Bernard

2016-08-01

We aimed to evaluate early recanalization postintravenous (i.v.) tissue plasminogen activator (t-PA) by digital subtraction angiography (DSA) in acute ischemic stroke (AIS) with large vessel occlusion (LVO). We performed baseline CT angiography to identify LVO in AIS. Recanalization pre- and post-intra-arterial therapy (IAT) was categorized to none, partial, and global recanalization (GR). Modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Among 1610 patients with AIS, 286 received IV t-PA. Of these, 55 patients with LVO were included. The median time from IV t-PA to DSA was 120 min (interquartile range, 79-152). Recanalization post-IV t-PA was observed in seven patients (12.7%). By occlusion sites, the recanalization rates were as follows: extracranial internal carotid artery 2 of 14 (14.3%); intracranial internal carotid artery 3 of 24 (12.5%); M1 of middle cerebral artery 3 of 39 (7.7%); M2 of middle cerebral artery 1 of 40 (2.5%); vertebral artery 0 of 4; and basilar artery 0 of 7. GR post-IAT was associated with favorable outcomes (odds ratio: 8.6; 95% confidence interval, 1.5-48.0; P = 0.014). Early recanalization assessed by DSA post-IV t-PA is rarely observed in acute ischemic stroke patients with LVO. © 2016 John Wiley & Sons Ltd.

Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of eukaryotic transcription factors, NF-kappaB and AP-1.

Science.gov (United States)

Surh, Y J; Han, S S; Keum, Y S; Seo, H J; Lee, S S

2000-01-01

Recently, considerable attention has been focused on identifying dietary and medicinal phytochemicals that can inhibit, retard or reverse the multi-stage carcinogenesis. Spices and herbs contain phenolic substances with potent antioxidative and chemopreventive properties. Curcumin, a yellow colouring agent from turmeric and capsaicin, a pungent principle of red pepper exhibit profound anticarcinogenic and antimutagenic activities. Two well-defined eukaryotic transcription factors, nuclear factor-kappa B (NF-kappaB) and activator protein 1 (AP-1) have been implicated in pathogenesis of many human diseases including cancer. These transcription factors are known to be activated by a wide array of external stimuli, such as tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), tumor necrosis factor, reactive oxygen species, bacterial lipopolysaccharide, and ultraviolet. In the present study, we found that topical application of TPA onto dorsal skin of female ICR mice resulted in marked activation of epidermal NF-kappaB and AP-1. Curcumin and capsaicin, when topically applied prior to TPA, significantly attenuated TPA-induced activation of each transcription factor in mouse skin. Likewise, both compounds inhibited NF-kappaB and AP-1 activation in cultured human promyelocytic leukemia (HL-60) cells stimulated with TPA. Based on these findings, it is likely that curcumin and capsaicin exert anti-tumor promotional effects through suppression of the tumor promoter-induced activation of transcription factors, NF-kappaB and AP-1.

High Energy Density Sciences with High Power Lasers at SACLA

Science.gov (United States)

Kodama, Ryosuke

2013-10-01

One of the interesting topics on high energy density sciences with high power lasers is creation of extremely high pressures in material. The pressures of more than 0.1 TPa are the energy density corresponding to the chemical bonding energy, resulting in expectation of dramatic changes in the chemical reactions. At pressures of more than TPa, most of material would be melted on the shock Hugoniot curve. However, if the temperature is less than 1eV or lower than a melting point at pressures of more than TPa, novel solid states of matter must be created through a pressured phase transition. One of the interesting materials must be carbon. At pressures of more than TPa, the diamond structure changes to BC and cubic at more than 3TPa. To create such novel states of matter, several kinds of isentropic-like compression techniques are being developed with high power lasers. To explore the ``Tera-Pascal Science,'' now we have a new tool which is an x-ray free electron laser as well as high power lasers. The XFEL will clear the details of the HED states and also efficiently create hot dense matter. We have started a new project on high energy density sciences using an XFEL (SACLA) in Japan, which is a HERMES (High Energy density Revolution of Matter in Extreme States) project.

VEGF Correlates with Inflammation and Fibrosis in Tuberculous Pleural Effusion

Science.gov (United States)

Bien, Mauo-Ying; Wu, Ming-Ping; Chen, Wei-Lin; Chung, Chi-Li

2015-01-01

Objective. To investigate the relationship among angiogenic cytokines, inflammatory markers, and fibrinolytic activity in tuberculous pleural effusion (TBPE) and their clinical importance. Methods. Forty-two patients diagnosed with TBPE were studied. Based on chest ultrasonography, there were 26 loculated and 16 nonloculated TBPE 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. 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 lactate dehydrogenase (LDH), VEGF, IL-8, PAI-1, and PAI-1/tPA ratio were significantly higher, while effusion glucose, pH value, and tPA were significantly lower, in loculated than in nonloculated TBPE. VEGF and IL-8 correlated positively with LDH and PAI-1/tPA ratio and negatively with tPA in both loculated and nonloculated TBPE. Patients with higher VEGF or greater effusion size were prone to develop RPT (n = 14; VEGF, odds ratio 1.28, P = 0.01; effusion size, odds ratio 1.01, P = 0.02), and VEGF was an independent predictor of RPT in TBPE (receiver operating characteristic curve AUC = 0.985, P Effusion VEGF correlates with pleural inflammation and fibrosis and may be targeted for adjunct therapy for TBPE. PMID:25884029

VEGF correlates with inflammation and fibrosis in tuberculous pleural effusion.

Science.gov (United States)

Bien, Mauo-Ying; Wu, Ming-Ping; Chen, Wei-Lin; Chung, Chi-Li

2015-01-01

To investigate the relationship among angiogenic cytokines, inflammatory markers, and fibrinolytic activity in tuberculous pleural effusion (TBPE) and their clinical importance. Forty-two patients diagnosed with TBPE were studied. Based on chest ultrasonography, there were 26 loculated and 16 nonloculated TBPE 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. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up. The effusion size and effusion lactate dehydrogenase (LDH), VEGF, IL-8, PAI-1, and PAI-1/tPA ratio were significantly higher, while effusion glucose, pH value, and tPA were significantly lower, in loculated than in nonloculated TBPE. VEGF and IL-8 correlated positively with LDH and PAI-1/tPA ratio and negatively with tPA in both loculated and nonloculated TBPE. Patients with higher VEGF or greater effusion size were prone to develop RPT (n=14; VEGF, odds ratio 1.28, P=0.01; effusion size, odds ratio 1.01, P=0.02), and VEGF was an independent predictor of RPT in TBPE (receiver operating characteristic curve AUC=0.985, PEffusion VEGF correlates with pleural inflammation and fibrosis and may be targeted for adjunct therapy for TBPE.

Public Auditing and Data Dynamics in Cloud with Performance Assessment on Third Party Auditor

DEFF Research Database (Denmark)

P. Sawant, Snehal; Deshmukh, Aaradhana A.; Mihovska, Albena Dimitrova

2016-01-01

presented in this paper uses the concept of an external Third Party Auditor (TPA). TPA is an external party who is going to perform integrity verification of the user’s data on behalf of the user. The proposed scheme assures integrity verification with a dynamic data support, to ensure that changes made...

Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

NARCIS (Netherlands)

Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

2002-01-01

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

The "Propeller" incision for transpalatal advancement pharyngoplasty: a new approach to reduce post-operative oronasal fistulae.

Science.gov (United States)

Shine, Neville Patrick; Lewis, Richard Hamilton

2008-09-01

To present a new soft tissue approach for transpalatal advancement pharyngoplasty (TPA), the propeller incision, and to compare the rates of post-operative oronasal fistula in those undergoing TPA with the traditional "Gothic Arch" incision described by Woodson and those with the propeller incision. A prospectively maintained adult sleep apnoea surgery database was used to identify those patients undergoing TPA, either alone or in combination with other procedures, for obstructive sleep apnoea syndrome (OSAS) between February 2001 and September 2006 in a tertiary referral centre by a single surgeon (RHL). In addition to the incision used during TPA, patient demographic data, previous surgery of the upper airways, smoking history, pre-operative body mass index, respiratory disturbance index, oxygen saturation index and the occurrence of oronasal fistula post-operatively, were recorded. The propeller incision technique is described. A total of 89 patients who underwent TPA were identified. A total of 49 patients had a "Gothic Arch" incision and 40 had a "Propeller" incision. The two groups of patients were comparable in age, sex, previous tonsillar and uvulopalatopharyngoplasty surgery, smoking histories and pre-operative disease severity. In the "Gothic Arch" group, eight patients (16%) developed oronasal fistulae in the post-operative period versus only one patient (2.5%) in the "Propeller" group. The difference between the two groups was statistically significant (P=0.038, Fisher's exact test). Of the total cases with post-operative oronasal fistula (n=9), only one patient (from the Gothic Arch incision group) required operative closure which was performed under local anesthesia and healed without complication. The propeller incision provides an anatomically sensible axial-based flap that provides adequate access to perform TPA. It is associated with a lower incidence of oronasal fistula and is recommended by the authors.

Synthesis and Performance of Highly Stable Star-Shaped Polyaniline Electrochromic Materials with Triphenylamine Core

Science.gov (United States)

Xiong, Shanxin; Li, Shuaishuai; Zhang, Xiangkai; Wang, Ru; Zhang, Runlan; Wang, Xiaoqin; Wu, Bohua; Gong, Ming; Chu, Jia

2018-02-01

The molecular architecture of conducting polymers has a significant impact on their conjugated structure and electrochemical properties. We have investigated the influence of star-shaped structure on the electrochemical and electrochromic properties of polyaniline (PANI). Star-shaped PANI (SPANI) was prepared by copolymerization of aniline with triphenylamine (TPA) using an emulsion polymerization method. With addition of less than 4.0 mol.% TPA, the resulting SPANI exhibited good solubility in xylene with dodecylbenzenesulfonic acid (DBSA) as doping acid. The structure and thermal stability of the SPANI were characterized using Fourier-transform infrared spectroscopy, Raman spectroscopy, and thermogravimetric analysis, and the electrochemical behavior was analyzed by cyclic voltammetry (CV). The electrochromic properties of SPANI were tested using an electrochemical workstation combined with an ultraviolet-visible (UV-Vis) spectrometer. The results show that, with increasing TPA loading, the thermal stability of SPANI increased. With addition of 4.0 mol.% TPA, the weight loss of SPANI was 36.9% at 700°C, much lower than the value of 71.2% for PANI at the same temperature. The low oxidation potential and large enclosed area of the CV curves indicate that SPANI possesses higher electrochemical activity than PANI. Enhanced electrochromic properties including higher optical contrast and better electrochromic stability of SPANI were also obtained. SPANI with 1.6 mol.% TPA loading exhibited the highest optical contrast of 0.71, higher than the values of 0.58 for PANI, 0.66 for SPANI-0.4%, or 0.63 for SPANI-4.0%. Overdosing of TPA resulted in slow switching speed due to slow ion transport in short branched chains of star-shaped PANI electrochromic material. Long-term stability testing confirmed that all the SPANI-based devices exhibited better stability than the PANI-based device.

Rescue localized intra-arterial thrombolysis for hyperacute MCA ischemic stroke patients after early non-responsive intravenous tissue plasminogen activator therapy

International Nuclear Information System (INIS)

Kim, Dong Joon; Kim, Dong Ik; Kim, Seo Hyun; Lee, Kyung Yeol; Heo, Ji Hoe; Han, Sang Won

2005-01-01

The outcome of patients who show no early response to intravenous (i.v.) tissue plasminogen activator (tPA) therapy is poor. The objective of this study was to evaluate the feasibility of rescue localized intra-arterial thrombolysis (LIT) therapy for acute ischemic stroke patients after an early non-responsive i.v. tPA therapy. Patients with proximal MCA occlusions who were treated by LIT (n=10) after failure of early response [no improvement or improvement of National Institute of Health Stroke Scale (NIHSS) scores of ≤3] to i.v. tPA therapy (0.9 mg/kg - 10% bolus and 90% i.v. infusion over 60 min) were selected. The recanalization rates, incidence of post-thrombolysis hemorrhage and clinical outcomes [baseline and discharge NIHSS scores, mortality, 3 months Barthel index (BI) and modified Rankin score (mRS)] were evaluated. Rescue LIT therapy was performed on ten MCA occlusion patients (male:female=3:7, mean age 71 years). The mean time between the initiation of i.v. tPA therapy and the initiation of intra-arterial urokinase (i.a. UK) was 117±25.0 min [time to i.v. tPA 137±32 min; time to digital subtraction angiography (DSA) 221±42 min; time to i.a. UK 260±46 min]. The baseline NIHSS scores showed significant improvement at discharge (median from 18 to 6). Symptomatic hemorrhage and, consequent, mortality were noted in 2/10 (20%) patients. Three months good outcome was noted in 4/10 (40%, mRS 0-2) and 3/10 (30%, BI ≥95). In conclusion, rescue LIT therapy can be considered as a treatment option for patients not showing early response to full dose i.v. tPA therapy. Larger scale studies for further validation of this protocol may be necessary. (orig.)

Differential Regulation of PAI-1 in Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever With Renal Syndrome

OpenAIRE

Bellomo, Carla; Korva, Miša; Papa, Anna; Mäkelä, Satu; Mustonen, Jukka; Avšič-Županc, Tatjana; Vaheri, Antti; Martinez, Valeria P; Strandin, Tomas

2018-01-01

Abstract We analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)–1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of tPA commonly increased in both diseases, whereas PAI-1 correlated with disease severity in HCPS but not in HFRS.

Solvent effect on thermodynamics of Ag(I) coordination to tripodal polypyridine ligands

DEFF Research Database (Denmark)

Del Piero, Silvia; Melchior, Andrea; Menotti, Davide

2009-01-01

  An investigation on the thermodynamics of complex formation between Ag(I) ion and different tripodal ligands (tris[(2-pyridyl)methyl]amine) (TPA) and 6,6'-bis[bis(2-pyridylmethyl)aminomethyl]-2,2'-bipyridine (BTPA) has been carried out in the aprotic solvents dimethylsulfoxide (DMSO) and dimeth......  An investigation on the thermodynamics of complex formation between Ag(I) ion and different tripodal ligands (tris[(2-pyridyl)methyl]amine) (TPA) and 6,6'-bis[bis(2-pyridylmethyl)aminomethyl]-2,2'-bipyridine (BTPA) has been carried out in the aprotic solvents dimethylsulfoxide (DMSO......)ethyl)amine  (Me3TREN) as a result of  combination of structural rigidity of TPA and lower s-donor ability of pyridinic moieties with respect to primary and secondary amines. The same trend is found if the stability of Ag(I) complex with TPA is compared with that of tris(2-(dimethylamino)ethyl)amine  (ME6TREN...... is largely influenced by the different solvational properties of the solvents towards Ag(I) ion rather than by the significative difference in the dielectric constants. Udgivelsesdato: Oktober...

Temporal pole signal abnormality on MR imaging in temporal lobe epilepsy with hippocampal sclerosis: a fluid-attenuated inversion-recovery study; Anormalidade de sinal na imagem por RM do polo temporal na epilepsia do lobo temporal com esclerose hipocampal: um estudo pela sequencia inversao recuperacao com supressao da agua livre (FLAIR)

Energy Technology Data Exchange (ETDEWEB)

Carrete Junior, Henrique; Abdala, Nitamar; Szjenfeld, Jacob; Nogueira, Roberto Gomes [Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo, SP (Brazil). Dept. de Diagnostico por Imagem; Lin, Katia; Caboclo, Luis Otavio; Centeno, Ricardo Silva; Sakamoto, Americo Ceiki; Yacubian, Elza Marcia Targas [Universidade Federal de Sao Paulo (UNIFESP-EPM), Sao Paulo, SP (Brazil). Dept. de Neurologia e Neurocirurgia

2007-09-15

Objective: To determine the frequency and regional involvement of temporal pole signal abnormality (TPA) in patients with hippocampal sclerosis (HS) using fluid-attenuated inversion-recovery (FLAIR) MR imaging, and to correlate this feature with history. Method: Coronal FLAIR images of the temporal pole were assessed in 120 patients with HS and in 30 normal subjects, to evaluate gray-white matter demarcation. Results: Ninety (75%) of 120 patients had associated TPA. The HS side made difference regarding the presence of TPA, with a left side prevalence (p=0.04, {chi}{sup 2} test). The anteromedial zone of temporal pole was affected in 27 (30%) out of 90 patients. In 63 (70%) patients the lateral zone were also affected. Patients with TPA were younger at seizure onset (p=0.018), but without association with duration of epilepsy. Conclusion: Our FLAIR study show temporal pole signal abnormality in 3/4 of patients with HS, mainly seen on the anteromedial region, with a larger prevalence when the left hippocampus was involved. (author)