The M358R variant of α_1-proteinase inhibitor inhibits coagulation factor VIIa

International Nuclear Information System (INIS)

Sheffield, William P.; Bhakta, Varsha

2016-01-01

The naturally occurring M358R mutation of the plasma serpin α_1-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg–Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg–Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10"2 M"−"1sec"−"1. We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin. - Highlights: • The inhibitory specificity of the serpin alpha-1-proteinase inhibitor (API) is sharply altered in the M358R variant. • API M358R forms denaturation-resistant complexes with coagulation factor VIIa at a rate accelerated by tissue factor but unaffected by heparin. • Complex formation was shown by gel-based assays and quantified kinetically by inhibition of FVIIa-dependent amidolysis.

Myosin VIIa as a common component of cilia and microvilli.

Science.gov (United States)

Wolfrum, U; Liu, X; Schmitt, A; Udovichenko, I P; Williams, D S

1998-01-01

The distribution of myosin VIIa, which is defective or absent in Usher syndrome 1B, was studied in a variety of tissues by immunomicroscopy. The primary aim was to determine whether this putative actin-based mechanoenzyme is a common component of cilia. Previously, it has been proposed that defective ciliary function might be the basis of some forms of Usher syndrome. Myosin VIIa was detected in cilia from cochlear hair cells, olfactory neurons, kidney distal tubules, and lung bronchi. It was also found to cofractionate with the axonemal fraction of retinal photoreceptor cells. Immunolabeling appeared most concentrated in the periphery of the transition zone of the cilia. This general presence of a myosin in cilia is surprising, given that cilia are dominated by microtubules, and not actin filaments. In addition to cilia, myosin VIIa was also found in actin-rich microvilli of different types of cell. We conclude that myosin VIIa is a common component of cilia and microvilli.

The M358R variant of α{sub 1}-proteinase inhibitor inhibits coagulation factor VIIa

Energy Technology Data Exchange (ETDEWEB)

Sheffield, William P., E-mail: sheffiel@mcmaster.ca [Canadian Blood Services, Centre for Innovation, Hamilton, Ontario (Canada); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario (Canada); Bhakta, Varsha [Canadian Blood Services, Centre for Innovation, Hamilton, Ontario (Canada)

2016-02-12

The naturally occurring M358R mutation of the plasma serpin α{sub 1}-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg–Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg–Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10{sup 2} M{sup −1}sec{sup −1}. We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin. - Highlights: • The inhibitory specificity of the serpin alpha-1-proteinase inhibitor (API) is sharply altered in the M358R variant. • API M358R forms denaturation-resistant complexes with coagulation factor VIIa at a rate accelerated by tissue factor but unaffected by heparin. • Complex formation was shown by gel-based assays and quantified kinetically by inhibition of FVIIa-dependent amidolysis.

Perturbation fields in W VII-AS and Helias configurations

International Nuclear Information System (INIS)

Harmeyer, E.; Kisslinger, J.; Montvai, A.; Rau, F.; Wobig, H.

1988-01-01

Effects of pertubed topologies of the W VII-AS vacuum fields on the configuration with rational and irrational rotational transform are illustrated. Even small perturbation fields are unacceptable at rational values of the rotational transform. For example at a rotational transform = 1/2 in W VII-AS, when exceeding an effective homogeneous Bx/B = 3 x 10 -4 , the size of the rotational transform = 1/2 = 5/10 islands is doubled. At irrational values a Bx/B = 1/2% shows tolerable effects, for both W VII-AS and HS4-12. At rational values of the rotational transform = 1 near the edge, Bx/B values = 1/4 to 1/8% show a rather large increase of the aspect ratio, so an edge value of rotational transform = 1 should be avoided

A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

DEFF Research Database (Denmark)

Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

2007-01-01

Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

Wendelstein VII-A in torsatron mode

International Nuclear Information System (INIS)

Harmeyer, E.; Kisslinger, J.; Rau, F.; Wobig, H.

1985-03-01

Variable shear - positive or negative, up to about 20 percent - can be introduced into the Wendelstein VII-A Stellarator vacuum field configuration by different currents in the two helix systems, and balancing the resulting vertical field. (orig.)

Vacunas de bacterias recombinantes vivas

OpenAIRE

Blanco León, Marina

2016-01-01

La vacunación es uno de los logros más importantes en la historia de la medicina, que ha ido evolucionando a lo largo de los años permitiendo una reducción significativa de la mortalidad infantil, una disminución de la incidencia de enfermedades e incluso la erradicación de algunas de ellas en países enteros. Las vacunas de nueva generación surgen para reducir o eliminar las carencias de las vacunas “tradicionales”. Técnicas biotecnológicas basadas en el ADN recombinante han dado lugar, entre...

Producción de proteínas recombinantes de Plasmodium falciparum en Escherichia coli

Directory of Open Access Journals (Sweden)

Ángela Patricia Guerra

2016-04-01

Conclusión. El uso de cepas de E. coli genéticamente modificadas fue fundamental para alcanzar altos niveles de expresión de las cuatro proteínas recombinantes evaluadas y permitió obtener dos de ellas en forma soluble. La estrategia utilizada permitió expresar cuatro proteínas recombinantes de P. falciparum en cantidad suficiente para inmunizar ratones y producir anticuerpos policlonales y, además, conservar proteína pura y soluble de dos de ellas para ensayos futuros.

Postpartum hemorrhage in a Jehovah's Witness patient controlled with Tisseel, tranexamic acid, and recombinant factor VIIa.

Science.gov (United States)

Arab, Tarek Samir; Al-Wazzan, Ahmad Bakr; Maslow, Ken

2010-10-01

The management of a patient refusing blood transfusion who subsequently experiences a severe postpartum hemorrhage is a particular clinical challenge. A 30-year-old nulliparous patient (who was a Jehovah's Witness) had labour induced for post-dates at 41+4 weeks' gestational age after an uncomplicated pregnancy. She delivered by Caesarean section for dystocia and suspected chorioamnionitis, and subsequently developed postpartum hemorrhage that required management with oxytocin, ergometrine, carboprost, uterine artery ligation, and Hayman compression sutures. The patient ultimately required two additional visits to the operating room, culminating in hysterectomy. Use of tranexamic acid, recombinant factor VIIa, and Tisseel was instrumental in halting the ongoing hemorrhage. Optimal management of a patient refusing administration of blood products requires a multidisciplinary approach as well as a combination of traditional and novel therapies.

Human myosin VIIa is a very slow processive motor protein on various cellular actin structures.

Science.gov (United States)

Sato, Osamu; Komatsu, Satoshi; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Tanaka, Ryosuke; Mizutani, Takeomi; Watanabe, Tomonobu M; Ikebe, Reiko; Ikebe, Mitsuo

2017-06-30

Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. Although it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7AΔTail/LZ) at the single-molecule level. We found that the HM7AΔTail/LZ moves processively on single actin filaments with a step size of 35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4 s, yielding ∼0.3 s -1 for the mechanical turnover rate; hence, the velocity of HM7AΔTail/LZ was extremely slow, at 11 nm·s -1 We also examined HM7AΔTail/LZ movement on various actin structures in demembranated cells. HM7AΔTail/LZ showed unidirectional movement on actin structures at cell edges, such as lamellipodia and filopodia. However, HM7AΔTail/LZ frequently missed steps on actin tracks and exhibited bidirectional movement at stress fibers, which was not observed with tail-truncated myosin Va. These results suggest that the movement of the human myosin VIIa motor protein is more efficient on lamellipodial and filopodial actin tracks than on stress fibers, which are composed of actin filaments with different polarity, and that the actin structures influence the characteristics of cargo transportation by human myosin VIIa. In conclusion, myosin VIIa movement appears to be suitable for translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Produção de proteínas recombinantes por plantas transgénicas

OpenAIRE

Filipe, Ana Patrícia da Costa

2015-01-01

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz O desenvolvimento da tecnologia de ADN recombinante permite a introdução de genes exógenos de interesse em células de diferentes sistemas de expressão com o fim de obtenção de características desejáveis. As plantas transgénicas têm sido desenvolvidas para o melhoramento agrícola, para a produção de alimentos funcionais, e mais recentemente, para a produção de proteínas recombinantes. A utiliza...

Avaliação do antígeno SAG2a recombinante de Toxoplasma gondii como um potencial marcador diagnóstico para Toxoplasmose humana aguda

OpenAIRE

Béla, Samantha Ribeiro

2007-01-01

Proteínas recombinantes têm sido utilizadas para o diagnóstico sorológico da infecção por Toxoplasma gondii para diferenciar entre as fases aguda e crônica da toxoplasmose. Neste estudo, foi avaliada a reatividade de anticorpos IgG e IgG1 através de imunoensaios em soros de pacientes com toxoplasmose aguda e crônica dirigidos contra dois antígenos recombinantes clonados e expressos em E. coli, SAG2A (molécula recombinante total) e SAG2A(DELTA) (molécula recombinante deletada do...

Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry

DEFF Research Database (Denmark)

Song, Hongjian; Olsen, Ole H; Persson, Egon

2014-01-01

Factor VIIa (FVIIa) is a trypsin-like protease which plays an important role in initiating blood coagulation. Very limited structural information is available for the free, inactive form of FVIIa that circulates in the blood prior to vascular injury and the molecular details of its activity...... signal extends to the EGF1 domain in the light chain of FVIIa, underscoring a remarkable intra- and interdomain allosteric regulation of this trypsin-like protease....

Role of hepsin in factor VII activation in zebrafish.

Science.gov (United States)

Khandekar, Gauri; Jagadeeswaran, Pudur

2014-01-01

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

Transmission lines and launching systems for ECRH on the garching stellarators W VIIa and W VII-AS

International Nuclear Information System (INIS)

Thumm, M.; Janzen, G.; Mueller, G.; Schueller, P.G.; Wilhelm, R.; Erckmann, V.

1983-01-01

The transmission lines and launching systems for non ohmic plasma production and heating by ECR-waves at 28 GHz (200 kW, 40 ms) and 70 GHz (200 kW, 100 ms) in the Garching Wendelstein Stellarator W VIIa and at 70 GHz (800 kW, cw) in the future Advanced Stellarator W VII-AS are described. The ECRH systems meet the requirements for neutral gas breakdown (R-wave), heating of a cold plasma (X-mode) and heating of a warm plasma (0-mode) in a combined way. Periodically modulated wall mode converters (sinusoidal m=0 radius modulation, a 0 =31.75 mm at 28 GHz, a 0 =13.9 mm at 70 GHz) convert the circular electric TE/sub on/ gyrotron output mode mixture (mainly TE 02 mode) into a pure TE 01 wave which is used for the long distance transmission in smooth overmoded waveguides (I.D. = 63.5 mm). At the converter inputs the phases between the TE/sub on/ modes are matched by phase shifters. The measured conversion efficiency for characteristic mode mixtures (TE 02 /TE 01 /TE 03 ) at 28 GHz is about 98 %. For the geometrical and electrical matching of different waveguide diameters waveguide tapers with approximate Tschebycheff mode-conversion responses are used

Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle

Science.gov (United States)

Boëda, Batiste; El-Amraoui, Aziz; Bahloul, Amel; Goodyear, Richard; Daviet, Laurent; Blanchard, Stéphane; Perfettini, Isabelle; Fath, Karl R.; Shorte, Spencer; Reiners, Jan; Houdusse, Anne; Legrain, Pierre; Wolfrum, Uwe; Richardson, Guy; Petit, Christine

2002-01-01

Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia. PMID:12485990

Interacciones de las proteínas disulfuro isomerasa y de choque térmico Hsc70 con proteínas estructurales recombinantes purificadas de rotavirus

Directory of Open Access Journals (Sweden)

Luz Y. Moreno

2016-01-01

Full Text Available Introducción. La entrada de rotavirus a las células parece estar mediado por interacciones secuenciales entre las proteínas estructurales virales y algunas moléculas de la superficie celular. Sin embargo, los mecanismos por los cuales el rotavirus infecta la célula diana aún no se comprenden bien. Existe alguna evidencia que muestra que las proteínas estructurales de rotavirus VP5* y VP8* interactúan con algunas moléculas de la superficie celular. La disponibilidad de las proteínas estructurales de rotavirus recombinantes en cantidad suficiente se ha convertido en un aspecto importante para la identificación de las interacciones específicas de los receptores virus-célula durante los eventos tempranos del proceso infeccioso. Objetivo. El propósito del presente trabajo es realizar un análisis de las interacciones entre las proteínas estructurales de rotavirus recombinante VP5*, VP8* y VP6, y las proteínas celulares Hsc70 y PDI utilizando sus versiones recombinantes purificadas. Materiales y métodos. Las proteínas recombinantes de rotavirus VP5* y VP8* y las proteínas recombinantes celulares Hsc70 y PDI se expresaron en E. coli BL21 (DE3, mientras que VP6 se expresó en células MA104 con virus vaccinia recombinante transfectada. La interacción entre el rotavirus y las proteínas celulares se estudió mediante ELISA, co-inmunoprecipitación y SDS-PAGE/ Western. Resultados. Las condiciones óptimas para la expresión de proteínas recombinantes se determinaron y se generaron anticuerpos contra ellas. Los resultados sugirieron que las proteínas virales rVP5* y rVP6 interactúan con Hsc70 y PDI in vitro. También se encontró que éstas proteínas virales recombinantes interactúan con Hsc70 en las balsas lipídicas (“Rafts” en un cultivo celular. El tratamiento de las células, ya sea con DLP o rVP6 produjo significativamente la inhibición de la infección por rotavirus. Conclusión. Los resultados permiten concluir que r

Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

International Nuclear Information System (INIS)

Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

1990-01-01

The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

Confinement of Stellarator plasmas with neutral beam and RF heating in W VII-A

International Nuclear Information System (INIS)

Grieger, G.; Cattanei, G.; Dorst, D.

1986-01-01

WENDELSTEIN VII-A has been operated for ten years. It is a low-shear, high-aspect-ratio device. The confinement properties have been thoroughly studied for both ohmically heated and net-current free plasmas. For the latter case, NBI- and ECF-maintained plasmas were of particular importance. It was found that under optimized conditions the core of high-pressure, net-current free plasmas is mainly governed by collisional effects. The experiment will now be shut down for upgrading it into the Advanced Stellarator WEDNDELSTEIN VII-AS. (author)

Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

DEFF Research Database (Denmark)

Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

2004-01-01

Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role...... in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

Comparative Biochemical and Functional Studies on a Branded Human Recombinant Factor VIIa and a Biosimilar Equivalent Product.

Science.gov (United States)

Sadeghi, Nasiredin; Kahn, Daniel; Syed, Daneyal; Iqbal, Omer; Abro, Schuharazad; Eshraghi, Reza; Hoppensteadt, Debra; Fareed, Jawed

2014-09-01

Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) is used to control bleeding in patients with hemophilia. A generic version of FVIIa was developed by AryoGen (Tehran, Iran). This study compared the composition and functional activities of AryoSeven and NovoSeven. Each product was compared at equigravimetric (1 mg/mL) stock solution for protein content. The proteomic profile was obtained using surface-enhanced laser desorption ionization mass spectrometry. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis was carried out to determine the protein profile and Western blotting was performed using a polyclonal rabbit antihuman FVIIa antibody. The FVIIa-related antigen was also measured using a commercially available enzyme-linked immunosorbent assay method. Functional assay included the prothrombin time correction in FVII-deficient plasma. The protein content was comparable in 2 products and the mass spectra analysis showed a single peak at 50 kDa in all products. The SDS-PAGE and immunoblotting studies were comparable. Both products exhibited similar coagulant properties in different assays. © The Author(s) 2014.

Vectores recombinantes basados en el virus modificado de ankara (MVA) como vacunas preventivas y terapéuticas contra el SIDA

OpenAIRE

Heeney, Jonathan L.; Mooij, Petra; Nájera García, José Luis; Jiménez, Victoria; Esteban, Mariano; Gómez, Carmen E.

2005-01-01

Vectores Recombinantes basados en el Virus Modificado de Ankara (MVA) como Vacunas Preventivas y Terapéuticas contra el SIDA. Losvirus recombinantes de la invención contienen secuencias que se encuentran insertadas en el mismo sitio de inserción del MVA y permiten la expresión simultánea de varios antígenos, una proteína Env del VIH-I consistente en una proteína gpl20 carente de secuencias correspondientes a la proteína gp41, y una proteína quiméricade fusión de Gag, Pol y Nef. Son virus esta...

Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.

Science.gov (United States)

el-Amraoui, A; Sahly, I; Picaud, S; Sahel, J; Abitbol, M; Petit, C

1996-08-01

Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks.

Vectores recombinantes basados en el virus modificado de Ankara (MVA) com vacunas preventivas y terapeúticas contra la hepatitis C

OpenAIRE

Esteban, Mariano; Gómez, Carmen E.; Perdiguero, Beatriz

2014-01-01

[ES] Los virus recombinantes de la invención contienen secuencias que se encuentran insertadas en el mismo sitio de inserción del MVA y que permiten la expresión simultáneamente de varios antígenos del VHC, concretamente las proteínas maduras estructurales (Core, E1, E2 y p7) y no estructurales (NS2, NS3, NS4A, NS4B, NS5A más los 201 aminoácidos de la región N-terminal de NS5B). Con ello se consiguen virus recombinantes estables, que permiten el desencadenamiento de una respuesta inmune contr...

Effect of Recombinant Factor VIIa as an Adjunctive Therapy in Damage Control for Wartime Vascular Injuries: A Case Control Study

Science.gov (United States)

2009-04-01

Axillary 1 1 2 4 Iliac 2 2 4 Profunda femoral 1 3 4 Femoral 3 1 1 1 2 1 8 Popliteal 1 2 3 Total 9 1 2 4 25 6 20 2 3 72 * Followed by SV graft...VIIa [database on the Internet ]: US Department of Defense. Available at: https://jpta.fhp.osd.mil. Accessed 2007. 10. Boffard KD, Riou B, Warren B, et al

Hindi tagandamine võib viia võimukoalitsiooni lagunemiseni Kohtla-Järvel / Erik Gamzejev

Index Scriptorium Estoniae

Gamzejev, Erik, 1967-

2003-01-01

Ilmunud ka: Severnoje Poberezhje 26. sept. lk. 1. Keskerakonna soov saada endale Kohtla-Järve linnapea ametikoht võib viia Keskerakonna ja endiste Res Publica liikmete vahel sõlmitud koalitsiooni lagunemiseni

Grindeks saab Tallinna Farmaatsiatehase börsilt ära viia / Sirje Rank

Index Scriptorium Estoniae

Rank, Sirje, 1966-

2005-01-01

Tallinna Farmaatsiatehase ostnud Läti Grindeks on kätte saanud vajalikud 95% aktsiatest, mis võimaldavad firma börsilt ära viia. Diagramm: Grindeksi käive ja aktsia. Vt. samas: Lauri Matsulevitsh. Investor teenis Grindeksiga 40 000 krooni

Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage

Directory of Open Access Journals (Sweden)

Eckman Mark H

2008-05-01

Full Text Available Abstract Background Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER given the poor neurologic outcomes after ICH with conventional management. Methods We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE. We assumed no substantial cost differences in care between the two strategies except: 1 cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408; 2 cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death; and 3 differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home, and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE. Results In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER Conclusion Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.

Uso de la estreptoquinasa recombinante cubana: Atención de enfermería

OpenAIRE

Arcia Lumpuy, Sofía; López Pedrosa, Gloria L

1995-01-01

Se realizan estudios y aplicación de agentes trombolíticos en las primeras horas de diagnosticado e instalado el infarto, con el objetivo de recuperar la reperfusión coronaria y preservar el músculo cardiaco. Se analiza el empleo de la estreptoquinasa recombinante cubana (heberkinasa) en ésta, que es la cuarta investigación sobre ella y su aplicación en los pacientes infartados.

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

Science.gov (United States)

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-12-15

Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

Technical progress report on Wendelstein VII-AS

International Nuclear Information System (INIS)

Sapper, J.

1985-01-01

The modification of the WENDELSTEIN experiment at Garching into an advanced version with modular design was approved in 1982, after a planning time of one and a half year. The essential components /1,2/ of the new WENDELSTEIN VII-AS device are: - A modular field system instead of a helix and TF-system, consisting of 45 nonplanar coils. - A modular vacuum vessel, adapted to the coil system. - An additional TF-system for t-variation, consisting of 10 plane coils. - A structure shell for the modular field coils so that the vessel is free of coil forces

Estrategias de obtención de proteínas recombinantes en Escherichia coli

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José García

2013-08-01

Full Text Available La expresión de proteínas recombinantes se ha favorecido con el uso de Escherichia coli debido a su relativo bajo costo, alta densidad de cultivo, su fácil manipulación genética y a las diversas herramientas biotecnológicas disponibles que son compatibles. En este artículo se presentan algunas estrategias para la expresión de Escherichia coli; se destacan factores genéticos y fisiológicos que incluyen: número de copias del vector de expresión, características del gen, estabilidad del ácido ribonucleico mensajero, promotor empleado, cepa utilizada, composición del medio de cultivo, parámetros de operación en el fermentador y también se abordan la conservación de cepas y la estrategia de cultivo y purificación.

Magnetic surfaces and localized perturbations in the Wendelstein VII-A stellarator

International Nuclear Information System (INIS)

Wobig, H.

1986-09-01

The critical dependence of plasma confinement in low-shear stellarators, such as Wendelstein VII-A, on the external rotational transform can be explained on the basis of magnetic surface destruction. External symmetry-breaking perturbations generate islands on the low order rational magnetic surfaces. The islands are largest at t=1/2 and t=1/3. Confinement is optimum in close proximity to these values. In order to study the structure of surfaces under the influence of perturbations, a mapping procedure is used instead of field line integration. It is found that the neighbourhood of low- order rational surfaces is particularly robust against surface destruction. The reason is that in this vicinity only rational surfaces with large m and n exist (t=m/n). On these surfaces the external perturbation only generates small islands. In W VII-A the current leads to the helical windings are one symmetry- breaking perturbation, and there might also be others. It is possible to avoid field errors of this kind in future stellarators. (orig.)

DESARROLLO DE UN POXVIRUS RECOMBINANTE QUE EXPRESA LA GLICOPROTEÍNA D DEL HERPESVIRUS BOVINO-1

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JULIÁN RUIZ SÁENZ

2012-09-01

Full Text Available El herpesvirus bovino-1 es un virus de genoma DNA perteneciente a la familia Herpesviridae, subfamilia Alfaherpesvinae, el cual afecta al bovino, en el que provoca un amplio espectro de manifestaciones clínicas, acarreando graves pérdidas económicas. El principal componente inmunogénico de su envoltura es la glicoproteína D (gD, la cual ha sido caracterizada y utilizada como inmunógeno en distintos sistemas de expresión. Diferentes estudios han demostrado la eficacia de los vectores poxvirales como un sistema eficiente para inmunizar animales contra diferentes antígenos. El objetivo de este trabajo fue generar un poxvirusrecombinante (Raccoonpox [RCN] que expresara una versión truncada de la gD del BHV-1 para ser usado como inmunógeno. Para ello, con ayuda de cebadores específicos se amplificó el gen que codifica para a versión truncada de la gD la cual no posee el dominio de anclaje de membrana (1,089 pares de bases, el cual posteriormente se clonó usando las enzimas EcoRI y BamHI en el plásmido de transferencia pTK/IRES/tpa que posee sitios de homología a la timidinakinasa del poxvirus, un sitio interno de entrada al ribosoma (IRES y una señal secretoria (tPA, generando el constructo pTK/gD/IRES/tpa. Para generar el RCN recombinante, se tomaron células de riñón de mono verde africano BSC-1, se infectaron con una cepa Silvestre del RCN (CDC/V71-I-85A a un Índice de Multiplicidad de Infección (MOI de 0,05, y se incubaron a 37ºC por 90 minutos; luego, las células fueron transfectadas con el constructo pTK/gD/IRES/tpa usando el sistema de transfección FuGENE 6®; generándose a través del sistema celular de recombinación de homólogos diferentes poblaciones virales con y sin el gen de interés. Para seleccionar los virus recombinantes que expresaban el gen de interés, se realizó una selección de recombinantes negativos para timidina kinasa y positivos para la gD por tres rondas de purificación de placas en monocapas

Toxicidad de δ-endotoxinas recombinantes de Bacillus thuringiensis sobre larvas de la polilla guatemalteca (Tecia solanivora (Lepidóptera: Gelechiidae

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Javier Hernández-Fernández

2008-07-01

Full Text Available Con el objetivo de determinar la actividad tóxica específica de las proteínas recombinantes Cry1Aa, Cry1Ac, Cry1B y Cry1C de Bacillus thuringiensis (Bt, sobre larvas de primer instar de Tecia solanivora se estableció la CL50 para las toxinas. Para este fin se implementó la cría masiva de este insecto bajo condiciones de laboratorio, 58±5% de humedad relativa, 18±5ºC de temperatura y un fotoperiodo de 23 h oscuridad y 1 h luz. Se utilizó una dieta seminatural consistente en láminas de papa variedad parda pastusa autoclavada con solución preservante (ácido ascórbico 7 g/L y metilparabeno 5 g/L, ya que fue estable en el tiempo, garantizó la reproducibilidad de los resultados y fue de fácil evaluación. Las proteínas recombinantes se evaluaron a una concentración de 0,1 μg/cm2. Los resultados obtenidos de porcentaje de mortalidad indicaron que no había diferencias entre las delta-endotoxinas recombinantes Cry1Aa, Cry1Ac, Cry1B y Cry1C de Bt (P

Cost-utility analysis of an adjunctive recombinant activated factor VIIa for on-demand treatment of bleeding episodes in dengue haemorrhagic fever.

Science.gov (United States)

Naing, Cho; Poovorawan, Yong; Mak, Joon Wah; Aung, Kyan; Kamolratankul, Pirom

2015-06-01

The present study aimed to assess the cost-utility analysis of using an adjunctive recombinant activated factor VIIa (rFVIIa) in children for controlling life-threatening bleeding in dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). We constructed a decision-tree model, comparing a standard care and the use of an additional adjuvant rFVIIa for controlling life-threatening bleeding in children with DHF/DSS. Cost and utility benefit were estimated from the societal perspective. The outcome measure was cost per quality-adjusted life years (QALYs). Overall, treatment with adjuvant rFVIIa gained QALYs, but the total cost was higher. The incremental cost-utility ratio for the introduction of adjuvant rFVIIa was $4241.27 per additional QALY. Sensitivity analyses showed the utility value assigned for calculation of QALY was the most sensitive parameter. We concluded that despite high cost, there is a role for rFVIIa in the treatment of life-threatening bleeding in patients with DHF/DSS.

Investigation of current drive possibilities with the present ICRH system in Wendelstein VII-AS

International Nuclear Information System (INIS)

Chiu, S.C.

1990-01-01

With the double antenna configuration, designed for first heating tests on W VII-AS, a maximum driven current of 390 A/MW coupled can be expected when using a frequency of 75 MHz and a phasing of π/2. (orig.)

The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Kazim, A.L.

1990-01-01

Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

Proteínas recombinantes útiles para el diagnóstico, prevención y estudios patogénicos de la leptospirosis : Estudio de mecanismos patogénicos involucrados

OpenAIRE

Prêtre, Gabriela

2011-01-01

Objetivo general El propósito general de este trabajo es: 1. Generar herramientas moleculares que sean útiles contra la leptospirosis, ya sea para su diagnóstico, prevención o un mejor conocimiento de su patogénesis. 2. Estudiar mecanismos patogénicos involucrados en la leptospirosis. Objetivos específicos 1. Clonado, expresión y purificación de proteínas recombinantes. 2. Producción de antisuero contra las proteínas recombinantes....

Neutron flux measurements at the Wendelstein VII-A stellarator

International Nuclear Information System (INIS)

Weller, A.; Maassberg, H.

1985-10-01

In addition to charge exchange analysis (CX) and charge exchange recombination spectroscopy (CXRS), the time evolution of the central ion temperature during neutral beam heated plasma discharges in the Wendelstein VII-A stellarator is derived from the neutron flux from thermal D-D reactions. In general, good quantitative agreement between the different methods is obtained. Neutron flux measurements also permit to investigate the slowing down of fast D + -ions from neutral beam injection (NBI). The results agree well with the predictions based on the assumption of a collisional slowing down mechanism. (orig.)

Current driven drift instability in the W VII-A stellarator

International Nuclear Information System (INIS)

Deutsch, R.; Wobig, H.

1978-12-01

The instability region and growth rates of current driven drift modes in the W VII-A stellarator are calculated. Several theoretical results are evaluated for specific temperature and density profiles. It is found that in the outer region of the plasma-column (r > 6 cm) collisional drift waves with wavelengths (k 2 x + K 2 y)sup(-1/2) = 0.13 - 0.3 cm exist. In this region also the electron thermal conductivity determined experimentally appears to be large. (orig./GG) [de

Factor VII and protein C are phosphatidic acid-binding proteins.

Science.gov (United States)

Tavoosi, Narjes; Smith, Stephanie A; Davis-Harrison, Rebecca L; Morrissey, James H

2013-08-20

Seven proteins in the human blood clotting cascade bind, via their GLA (γ-carboxyglutamate-rich) domains, to membranes containing exposed phosphatidylserine (PS), although with membrane binding affinities that vary by 3 orders of magnitude. Here we employed nanodiscs of defined phospholipid composition to quantify the phospholipid binding specificities of these seven clotting proteins. All bound preferentially to nanobilayers in which PS headgroups contained l-serine versus d-serine. Surprisingly, however, nanobilayers containing phosphatidic acid (PA) bound substantially more of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers containing PS. Consistent with this finding, liposomes containing PA supported higher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (factors X and Va, respectively) than did PS-containing liposomes. Moreover, treating activated human platelets with phospholipase D enhanced the rates of factor X activation by factor VIIa in the presence of soluble tissue factor. We hypothesize that factor VII and protein C bind preferentially to the monoester phosphate of PA because of its accessibility and higher negative charge compared with the diester phosphates of most other phospholipids. We further found that phosphatidylinositol 4-phosphate, which contains a monoester phosphate attached to its myo-inositol headgroup, also supported enhanced enzymatic activity of factor VIIa and activated protein C. We conclude that factor VII and protein C bind preferentially to monoester phosphates, which may have implications for the function of these proteases in vivo.

Rab GTPases Regulate Endothelial Cell Protein C Receptor-Mediated Endocytosis and Trafficking of Factor VIIa

Science.gov (United States)

Nayak, Ramesh C.; Keshava, Shiva; Esmon, Charles T.; Pendurthi, Usha R.; Rao, L. Vijaya Mohan

2013-01-01

Recent studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand complex. Rab GTPases are known to play a crucial role in the endocytic and exocytic pathways of receptors or receptor/ligand complexes. The present study was undertaken to investigate the role of Rab GTPases in the intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical vein endothelial cells (HUVEC) were transduced with recombinant adenoviral vectors to express wild-type, constitutively active, or dominant negative mutant of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescence confocal microscopy. In cells expressing wild-type or constitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its entry into the recycling endosomal compartment (REC) was inhibited. Expression of constitutively active Rab5A induced large endosomal structures beneath the plasma membrane where EPCR and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR-FVIIa. Expression of constitutively active Rab11 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internalized FVIIa into the REC. Expression of dominant negative Rab11 also inhibited the transport of FVIIa across the endothelium. Overall our data show that Rab GTPases regulate the internalization and intracellular trafficking of EPCR-FVIIa. PMID:23555015

Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

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H-Y Chou Sherry

2012-12-01

Full Text Available Abstract Background Recombinant factor VIIa (rFVIIa may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH, FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP and vitamin K alone. Methods We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%, deep venous thrombosis (DVT or pulmonary embolism (PE (22% vs 18%, coronary artery disease (CAD (38% vs 32%, and abnormal electrocardiogram (EKG (78% vs 85%. Troponin elevation following wICH was prevalent in both groups (47% vs 41%. Clinically significant myocardial infarction (MI, defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52. Past history of CAD (p=0.0061 and baseline abnormal EKG (p=0.02 were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18 and ischemic stroke (2% vs 0%; p=0.38 were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001 and 6 hours (p Conclusions Pre

Age-related changes in factor VII proteolysis in vivo.

Science.gov (United States)

Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

1996-08-01

Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

Analüütikud soovitavad Eesti Energia börsile viia / Piret Reiljan

Index Scriptorium Estoniae

Reiljan, Piret, 1983-

2008-01-01

Kohalikud analüütikud soovitavad viia Eesti Energia börsile, kuna see elavdaks aktsiaturgu ja tõmbaks ligi välisinvestoreid. Vt. samas: Raivo Vare: raske aeg töötab Eesti Energia börsiletoomise kasuks; Analüüs ootab pääsu valitsuskabinetti; Juhid ei püsi enam Eesti Energias. Diagrammid: Majandusnäitajad; Varade maht

INFECÇÃO EXPERIMENTAL DE BEZERROS COM RECOMBINANTES DO HERPESVÍRUS BOVINO TIPO 5 COM DELEÇÕES NOS GENES DA GLICOPROTEÍNA E, TIMIDINA QUINASE E AMBOS

OpenAIRE

Cyndia Mara Bezerra dos Santos

2010-01-01

O herpesvírus bovino tipo 5 (BoHV-5) é o agente de doença neurológica grave em bovinos. A utilização de vacinas recombinantes tem sido preconizada para o controle da infecção pelo BoHV-5. O objetivo do presente trabalho foi investigar a patogenia, em bezerros, de três recombinantes do BoHV-5, com deleções nos genes da glicoproteína E (BoHV-5gEΔ), da enzima timidina quinase (BoHV-5TKΔ) ou ambos (BoHV-5gETKΔ) para uso potencial em vacinas. Para isso, quatro grupos de bezerros com...

Somatotropina bovina recombinante en sincronización de estros y prolificidad de ovejas Pelibuey

OpenAIRE

Sosa-Pérez, G; Pérez-Hernández, P.; Vaquera-Huerta, H.; Salazar-Ortiz, J.; Sánchez-del-Real, C.; Cadena-Villegas, S.; Gallegos-Sánchez, J.

2014-01-01

Con la finalidad de estudiar si la administración de la Somatotropina Bovina Recombinante (bST) dos días antes del retiro del progestágeno, tiene efecto en la sincronización de estros, inicio del estro, fertilidad, prolificidad y tipo de parto en ovejas Pelibuey, a 180 ovejas de 4,0 ± 0,32 años de edad, se les inserto un dispositivo intravaginal impregnado con progesterona (CIDR P4 0,3 g), por nueve días. Dos días antes del retiro del dispositivo, las ovejas se asignaron aleatoriamente a uno ...

Effect of tearing modes on temperature and density profiles and on the perpendicular transport in the W VII-A stellarator

International Nuclear Information System (INIS)

Jaenicke, R.

1988-01-01

In the ohmically heated W VII-A stellarator, the behaviour of which is similar to that of a medium sized tokamak, the additional shearless external rotational transform t 0 (Δt 0 /t 0 0 perpendicular,e in a one-dimensional heat transport code. In this way, the measured temperature profiles can be reproduced quite well and the energy confinement time of discharges with tearing mode activity can be predicted quantitatively. The transport model is used to investigate the explicit dependence of κ perpendicular,e on the plasma current and to study the importance of plasma current driven instabilities for the energy confinement in the W VII-A stellarator as well as in tokamaks. (author). 19 refs, 14 figs

Análise de luteotrofina humana e de gonadotrofina coriônica humana, recombinante e natural, por cromatografia  líquida de alta eficiência em fase reversa

OpenAIRE

Beatriz Elane de Almeida

2009-01-01

Neste trabalho foram desenvolvidas condições específicas de RP-HPLC para análise de preparações recombinantes e naturais de hLH, de hCG, e de suas subunidades. O hLH e o hCG heterodimérico e suas subunidades e migraram com tempos de retenção (tR) significativamente diferentes, na seguinte ordem de hidrofobicidade crescente: -hCG < -hLH < hCG < hLH < -hCG < -hLH. Nestas condições, onze preparações foram estudadas: o Padrão Internacional recombinante hLH-WHO 96/602, uma preparação comercial r...

Neutral gas transport and particle recycling in the W VII-AS stellarator

International Nuclear Information System (INIS)

Sardei, F.; Ringler, H.; Dodhy, A.; Kuehner, G.

1990-01-01

Neutral gas transport simulations with the 3D DEGAS code were applied to model plasmas before the W VII-AS operation was started. For a source of neutrals due to limiter recycling the calculated neutral density distribution is strongly affected by the asymmetries of the magnetic flux surfaces, limiter and wall structures. For a typical ECF heated deuterium discharge from the first months of W VII-AS operation the time histories of H α signals at five toroidal positions provide information about the neutral fluxes due to limiter and wall recycling and to gas puffing. The H α signals are used to scale the calculated 3D distributions of the neutrals and the radial profiles of the ion sources as obtained from the DEGAS code. By comparing the results for the three different neutral sources the limiter is found to provide more than 80% of the plasma refuelling, with a recycling coefficient of about 95%. The calculated total particle fluxes resulting from the integrated ion sources are consistent with neoclassical predictions in the temperature gradient region. Near the plasma edge, however, the fluxes are strongly anomalous. The diffusion coefficient estimated from the fluxes and the measured density gradients (with z eff approx. 3) is about 1/10 - 1/20 of the electron heat conductivity. (author). 6 refs, 10 figs

Vectores recombinantes basados en el virus Vaccinia modificado de Ankara (MVA) como vacunas contra la leishmaniasis

OpenAIRE

Pérez Jiménez, Eva; Larraga, Vicente; Esteban, Mariano

2005-01-01

Vectores recombinantes basados en el virus vaccinia modificado de Ankara (MVA) como vacunas contra la leishmaniasis. Los vectores de la invención contienen secuencias codificantes de la proteína LACK, preferentemente insertadas en el locus de hemaglutinina del virus y bajo el control de un promotor que permite su expresión a lo largo del ciclo de infección del virus. Son vectores seguros, estables, que dan lugar a una potente respuesta inmune que confiere protección frente a la leishmaniasis,...

Estudio de inmunogenicidad para dos vacunas recombinantes contra hepatitis B

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O. Juliao

1991-12-01

Full Text Available Este estudio compara la inmunogenicidad (seroconversión, seroprotección e Hiperrespuesta, producida por dos vacunas recombinantes contra la hepatitis B (Engerix-B de Bélgica y Cubana, en dos esquemas (012 y 016 meses, empleando los métodos de cuantificación para Anti-HBsAg (Abbott y Organón, los cuales fueron también comparados. En el estudio participaron 257 voluntarios,  divididos al azar en 4 grupos (dos vacunas, dos esquemas. Resultados: los dos métodos de Abbon y Organon, no presentan diferencias estadísticas significativas. La vacuna cubana muestra una mayor respuesta inmunogénica para dos dosis de vacuna y para el esquema 012. No hay diferencia entre los esquemas 012 y 016 y en el esquema 016 no se ven diferencias estadísticamente significativas con la vacuna Engerix-B. En esta Última el esquema 016 muestra mejores resultados que el 012.

[Hemoglobins, XXXII. Analysis of the primary structure of the monomeric hemoglobin CTT VIIA (erythrocruorin) or Chironomus thummi thummi, Diptera (author's transl)].

Science.gov (United States)

Kleinschmidt, T; Braunitzer, G

1980-01-01

The dimeric hemoglobin CTT VIIA (erythrocruorin) was isolated from the hemolymph of the larva from Chironomus thummi thummi and purified by preparative polyacrylamide gel electrophoresis. Peptides obtained by limited tryptical digestion were sequenced by automatic Edman degradation. For the elucidation of the sequence in the C-terminal region of the chain, additional cleavages with proteinase of Staphylococcus aureus and chymotrypsin were necessary. CTT VIIA is compared with human beta-chains and other hemoglobins of Chironomus. The amino acid residues in the pocket are especially discussed. Most of them are invariant in all Chironomus hemoglobins, independent of the size of the heme pocket, which is normal in some components and enlarged in others.

Procedimiento para la obtención de levaduras vínicas superproductoras de manoproteínas mediante tecnologías no recombinantes

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Barcenilla Moraleda, José María; González Ramos, Daniel; Tabera, Laura; González García, Ramón

2008-01-01

Procedimiento para la obtención de levaduras vínicas superproductoras de manoproteínas mediante tecnologías no recombinantes. Procedimiento para obtener cepas de levaduras superproductoras de manoproteínas mediante la selección de mutantes resistentes a la toxina K9, cepas obtenibles por dicho procedimiento y usos.

Obtención y evaluación preliminar de un virus canarypox recombinante como candidato a vacuna antirrábica Development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate

OpenAIRE

Flavia Zanetti; Liliana Rudak; Matías Micucci; Daniela Conte Grand; Andrea Luque; Susana Russo; Oscar Taboga; Oscar Pérez; Gabriela Calamante

2012-01-01

En la Argentina, la rabia está circunscripta a algunas provincias del norte. La disponibilidad de nuevas vacunas que eliminen la manipulación del virus rábico y que permitan el control de la enfermedad es de importancia estratégica nacional y regional. Las vacunas basadas en poxvirus recombinantes se han utilizado con éxito como vacunas antirrábicas a nivel mundial. SI bien estos sistemas no están disponibles comercialmente, la plataforma de obtención de virus canarypox (CNPV) recombinantes y...

Clonamiento, expresión y seroreactividad del antígeno recombinante flagelina de Bartonella bacilliformis

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Karen Gallegos V

2005-03-01

Full Text Available Objetivos. Clonar el gen de la flagelina A (flaA de Bartonella bacilliformis, expresar y evaluar preliminarmente la seroreactividad de la proteína recombinante a sueros de pacientes con Bartonelosis por B. bacilliformis. Materiales y Métodos. Se diseñó una pareja de oligonucleótidos iniciadores -BbFlaA1 y BbFlaA2- para la amplificación del gen completo de la flagelina flaA de B. bacilliformis. El producto de amplificación obtenido se clonó en pGEM y luego se subclonó en el vector de expresión pGEX4T-1. Se indujo la expresión de la proteína de fusión rBbFlaA-GST con isopropil tio-β -D-galactosido (IPTG. La proteνna de fusiσn producida fue digerida con trombina para liberarla de GST. Finalmente, una prueba de ELISA fue estandarizada para detectar los anticuerpos IgG contra la proteína de fusión rBbFlaA-GST y rBbflaA libre de GST. Se evaluaron sueros de pacientes con diagnóstico de Bartonelosis por B. Bacilliformis (n= 30, sueros de individuos sanos (n= 20 y sueros de pacientes con otras enfermedades de posible reactividad cruzada; entre ellas, Brucelosis (n= 3, leptospirosis (n= 3 y salmonelosis (n=7. Resultados. Se determinó que para la expresión óptima en E. coli BL21 de la proteína de fusión rBbFlaA se requiere que el cultivo crezca en caldo LB/ampicilina a 30 °C suplementado con 2% de glucosa a partir de un preinóculo de 100 µL (crecido por toda la noche, hasta que alcance una densidad óptica de 1 OD600 y se induzca por dos horas con 2,5 mM de IPTG. Finalmente, el 57,6 % (17 de 30 sueros de pacientes con diagnóstico confirmado de bartonelosis reaccionaron con la proteína recombinante BbFlaA en el formato de ELISA. Conclusiones. Se logró expresar exitosamente en E. coli la proteína recombinante BbFlaA de B. bacilliformis, determinándose un protocolo de expresión y de purificación de rBbFlaA para la producción de esta proteína. Así también, el antígeno rBbFlaA es reconocido por anticuerpos de sueros de

Respuesta de IFN-y e Il-4 en ratones inoculados con una proteína G recombinante del virus de la rabia

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Edith Rojas-Anaya

2015-01-01

Full Text Available El objetivo de este estudio fue comparar el comportamiento de IFN-  e IL-4 en ratones inoculados con proteína G recombinante del virus de la rabia, que se expresa en maíz transgénico o baculovirus. Para este pr opósito, grupos de ratones se inocularon de la siguiente manera: Grupo 1, vacuna contra el virus de la rabia inactivado vía im; Grupo 2, proteína G recombinante deri vada de plantas por vía oral; Grupo 3, proteína G expresada en baculovirus vía im; Grupo 4, proteína G expresada en baculovirus por vía oral; Grupo 5, maíz no tran sformado por vía oral. Los niveles de IFN-  e IL-4 y los anticuerpos específicos se evaluaron cada 15 días. El desafío se realizó a los 60 días post inoculación (pi. Los grupos 1 y 3 promovieron un a mejor respuesta humoral. Por otro lado, los resultados demostraron que los mismos grupos mostraron los mejores niveles de IFN -  en el día 10 pi; mientras que la IL-4 se detectó en el día 15 pi. Para el estudio de supervivencia, el 83 % de los ratones inmunizados con vacuna inactivada, maíz y los inoculados im con extractos de baculovirus sob revivieron la infección viral. La proteína G de la rabia recombinante expresada en baculovirus promovió IFN-  y los anticuerpos de una manera similar a la vacuna de rabia inactivada. A pesar de esto los ratones alime ntados con maíz transgénico sobrevivieron al desafío en el mismo porcentaje que el grupo 3.

Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

International Nuclear Information System (INIS)

Rao, L.V.M.; Rapaport, S.I.

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue

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Liliana Morales

2017-01-01

Resultados. Los anticuerpos producidos fueron útiles en ensayos de Western blot e inmunofluorescencia y se reportó por primera vez un anticuerpo policlonal anti-NS3 que permitió la inmunoprecipitación de la proteína viral y la detecta con Western blot sin necesidad de inducir sobreexpresión de NS3 o de usar extractos de células marcados metabólicamente con radioisótopos. Conclusión. Las proteínas recombinantes expresadas y los anticuerpos producidos constituyen herramientas valiosas para estudiar procesos infecciosos del DENV que involucren a la proteína NS3 y evaluar pruebas dirigidas a interferir las funciones de esta proteína.

Análisis de plásmidos recombinantes con insertos de ADN genómico de Plasmodium falciparum

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Fernando Ángel S.

1988-06-01

Full Text Available Se describe la preparación de plásmidos pUC18 recombinantes provenientes de la construcción de una biblioteca genómica del parásito Plasmodium falciparum usando una modificación del método de lisis alcalina (1 . La cantidad de plásmido producido es suficiente para llevar a cabo varios análisis de digestión con enzimas de restricción y electroforesis en geles de agarosa.

Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

OpenAIRE

Rao, L V; Rapaport, S I

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry.

Science.gov (United States)

Song, Hongjian; Olsen, Ole H; Persson, Egon; Rand, Kasper D

2014-12-19

Factor VIIa (FVIIa) is a trypsin-like protease that plays an important role in initiating blood coagulation. Very limited structural information is available for the free, inactive form of FVIIa that circulates in the blood prior to vascular injury and the molecular details of its activity enhancement remain elusive. Here we have applied hydrogen/deuterium exchange mass spectrometry coupled to electron transfer dissociation to pinpoint individual residues in the heavy chain of FVIIa whose conformation and/or local interaction pattern changes when the enzyme transitions to the active form, as induced either by its cofactor tissue factor or a covalent active site inhibitor. Identified regulatory residues are situated at key sites across one continuous surface of the protease domain spanning the TF-binding helix across the activation pocket to the calcium binding site and are embedded in elements of secondary structure and at the base of flexible loops. Thus these residues are optimally positioned to mediate crosstalk between functional sites in FVIIa, particularly the cofactor binding site and the active site. Our results unambiguously show that the conformational allosteric activation signal extends to the EGF1 domain in the light chain of FVIIa, underscoring a remarkable intra- and interdomain allosteric regulation of this trypsin-like protease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparison of the calculated neutral beam shinethrough of the Wendelstein VII-A injection with calorimetric measurements

International Nuclear Information System (INIS)

Penningsfeld, F.P.

1987-06-01

Density profiles of the Wendelstein VII-A plasma as measured by Thomson scattering are used to calculate the temporally and spatially varying power density of the neutral beam shinethrough on the torus calorimeter for several shot series. The total energy deposited by the three beam species is obtained by integrating the transmitted power density in space and time. This global quantity is compared with the calorimetric measurements routinely performed for each shot. The agreement between calculated and measured energy is found to be ΔE/E = 2.3 ± 11% confirming the error estimation for the NEUDEN program used, which was only slightly modified to calculate the power density transmitted in the target plane. From this good agreement it is concluded that the program contains a realistic beam model and reliable cross-sections for the beam attenuation which is important for further applications. Furthermore, the same comparison was done with old results of the ODIN code by analyzing the corresponding raw data as far as they could be recovered, obtaining a similarly good consistency. A possible increase of 10 to 20% of the beam stopping cross section which could be expected for Wendelstein VII-A conditions by the effect of multistep collision processes as suggested by Boley et al. is discussed also. (orig.)

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C

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Yoan Antonio Sánchez Rodríguez

2011-03-01

Full Text Available INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal durante 48 semanas. RESULTADOS: el 88,5 % del total de casos presentó efectos adversos; de ellos el 79,5 % correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 % de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia.

INMUNOGENICIDAD DE LA PROTEÍNA RECOMBINANTE ASP1R DE Ancylostoma caninum EN UN MODELO MURINO

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Maria Giraldo G

2009-08-01

Full Text Available Objetivo. Construir un plásmido recombinante que exprese la proteína ASP1r de Ancylostoma caninum y evaluar su capacidad inmunogénica en un modelo murino. Materiales y métodos. Se realizó extracción de ARN de parásitos adultos de Ancylostoma caninum, se amplificó por RT –PCR el gen de la proteína ASP1. Este gen fue insertado en el vector pcDNA3. El inserto fue digerido con Bamh1 y EcoR1 y clonado direccionalmente. Posteriormente, se llevó a cabo transformación y selección de las células de E. coli DH5a competentes con el producto de la ligación. Se realizó un tamizaje por PCR confirmando la presencia del gen ASP1. El vector pcDNA3-ASP1 fue administrado vía intraglandular en la parotida e intramuscular en ratones Balb/c. En estos animales se les realizó determinación de anticuerpos en suero y saliva mediante las técnicas de ELISA e inmunohistoquímica. Resultados. Se determinó que el plásmido pcDNA3-ASP1 fue incorporado y expresado células E. coli DH5a. Este plásmido recombinante indujo la producción de anticuerpos Anti-ASP1 específicos en ratones Balb/c. Conclusiones. Se logró demostrar que la utilización de pcDNA3-ASP1 no produjo reacciones desfavorables en ratones Balb/c, además indujo respuesta humoral contra la proteína pcDNA3-ASP1 de excreción/secreción de Ancylostoma caninum en ratones.

Thermal analysis of W VII-AS limiter system and presentation of a graphite-block concept

International Nuclear Information System (INIS)

Mukherjee, S.; Grigull, P.

1989-01-01

A 2D-finite element thermal analysis of the initial W VII-AS limiter system has been performed and is discussed. Furhter to this analysis a graphite block concept is presented. This concept has been numerically analyzed for applications as a limiter in plasma and nuclear fusion experimental devices. The results are described in this paper. This block concept seems to be also applicable to first wall and divertor designs; the graphite elements could be replaced by ceramic ones. (author). 10 refs.; 13 figs

Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins.

Science.gov (United States)

Adato, A; Weil, D; Kalinski, H; Pel-Or, Y; Ayadi, H; Petit, C; Korostishevsky, M; Bonne-Tamir, B

1997-10-01

Usher syndrome types I (USH1A-USH1E) are a group of autosomal recessive diseases characterized by profound congenital hearing loss, vestibular areflexia, and progressive visual loss due to retinitis pigmentosa. The human myosin VIIA gene, located on 11q14, has been shown to be responsible for Usher syndrome type 1B (USH1B). Haplotypes were constructed in 28 USH1 families by use of the following polymorphic markers spanning the USH1B locus: D11S787, D11S527, D11S1789, D11S906, D11S4186, and OMP. Affected individuals and members of their families from 12 different ethnic origins were screened for the presence of mutations in all 49 exons of the myosin VIIA gene. In 15 families myosin VIIA mutations were detected, verifying their classification as USH1B. All these mutations are novel, including three missense mutations, one premature stop codon, two splicing mutations, one frameshift, and one deletion of >2 kb comprising exons 47 and 48, a part of exon 49, and the introns between them. Three mutations were shared by more than one family, consistent with haplotype similarities. Altogether, 16 USH1B haplotypes were observed in the 15 families; most haplotypes were population specific. Several exonic and intronic polymorphisms were also detected. None of the 20 known USH1B mutations reported so far in other world populations were identified in our families.

Uso de fator VII recombinante ativado para tratamento e profilaxia de grandes sangramentos Use of recombinant activated factor VII for treatment and prophylaxis of major bleeding

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Flávio Augusto Henriques Vince

2009-09-01

Full Text Available INTRODUÇÃO: O fator VII recombinante ativado (rFVIIa é uma proteína produzida por engenharia genética, cuja estrutura é muito semelhante à do fator VII intrínseco ativado (FVII. Sua ação se baseia no conhecimento do mecanismo de coagulação in vivo agindo na ativação direta do fator X resultando em formação independente de trombina no local da lesão e contribuindo dessa forma para formação de coágulo estável de fibrina sem a ação dos fatores VIII e IX. MÉTODOS: Foi realizada ampla revisão da literatura com o objetivo de determinar os achados recentes relacionados ao uso de fator VII recombinante ativado em pacientes com sangramento severo. RESULTADOS: Constatou-se que o uso de rFVIIa foi iniciado na década de 80 para profilaxia e tratamento de sangramento em pacientes com antecedente de hemofilia A ou B com inibidores de fator VIII e IX, deficiência de fator VII e trombastenia de Glanzmann refratários à reposição plaquetária. Em 1999 seu uso foi ampliado para outras situações clínicas e dessa forma, começaram a ser publicados diversos trabalhos mostrando a eficácia do rFVIIa como agente pró-hemostático em paciente com outras coagulopatias ou pacientes previamente hígidos com história de sangramento agudo de grande monta. Trauma é a principal causa de mortalidade no mundo sendo sangramento incontrolado o principal desafio no atendimento a estes pacientes. É comum a associação de trauma com coagulopatia, necessitando em algumas situações de terapia específica para o tratamento da mesma. Neste momento a terapia adjuvante com rFVIIa deve ser considerada. Outras causas comuns de sangramento são as operações cardíacas e ginecológicas/ obstétricas e doenças envolvendo o fígado. A coagulopatia nesses casos ocorre por deficiência dos fatores dependentes de vitamina K, sendo o FVII o com menor meia-vida. CONCLUSÃO: O uso de rFVIIa tem sido sugerido como opção terapêutica promissora para esses

Aplicación del análisis de riesgo a la producción de proteínas recombinantes expresadas en Escherichia coli

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José García

2012-04-01

Full Text Available En este trabajo se aplicó el análisis de riesgo, empleando la metodología de análisis de modos y efectos de fallas a los procesos de fermentación que utilizan la bacteria Esherichia coli como hospedero, para obtener proteínas recombinantes con fines terapéuticos, vacunales o diagnósticos. Se realizó el análisis del tipo y probabilidad de ocurrencia de las fallas en el proceso fermentativo, la evaluación del impacto en la calidad del mismo y la probabilidad de detección de dichas fallas. Se evaluó la severidad, probabilidad de ocurrencia y probabilidad de detección y se calculó el número de probabilidades de riesgo. Además, se emplearon técnicas utilizadas para el aseguramiento de la calidad como: tormenta de ideas y diagrama causa-efecto. Se concluye que las causas potenciales que tienen mayor influencia en las fallas de un proceso fermentativo de E. coli recombinante son: la inadecuada manipulación durante la inoculación, la presencia de fagos y el personal no calificado. Se proponen acciones a tomar para minimizar el riesgo.

RECOMBINANT FACTOR VIIa – NEW TREATMENT OPTION FOR CONTROL OF INTRACTABLE BLEEDING IN SURGICAL AND TRAUMA PATIENTS AND IN OTHER HAEMOSTASIS DISORDERS

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Samo Zver

2004-12-01

Full Text Available Background. Recombinant factor VIIa (rFVIIa, which is currently registered only for the treatment of haemophilia A and B patients with inhibitors, is seen increasingly as a possible universal haemostatic agent in untractable bleedings. One possible mechanism for the efficacy rFVIIa may be a consequence of it’s from the tissue factor (TF and from the level of disfunction in haemostatic system independant activity, which generates »thrombin burst« formation. It seems that rFVIIa remains active only at the site of tissue injury/bleeding.Conclusions. There are two components of bleeding in surgery and trauma patients. One is bleeding from large calibre arteries and veins which requires surgical intervention. The other, which goes along with the first one, is coagulopathic bleeding. The latter is a consequence of consumptional and dilutional coagulopathy, hypothermia, multitransfusion syndrom and metabolic disbalances in patients. rFVIIa effects coagulopathic component of the bleeding. For effective treatment with rFVIIa in such patients, replacement therapy with erythrocytes, platelets and fresh frozen plasma is mandatory and requires a haematologist assistance in the treatment strategy.Most reported cases of effective rFVIIa usage are from the field of traumatology. Until now, there have been no universal recommendations when to start treatment with rFVIIa in a bleeding trauma patient. Most experience with rFVIIa are from Israel and their recommendations are perhaps the most valuable ones. rFVIIa was used several times during intra-operative and post-operative bleeding episodes. There are reports of clinical studies and usage in patients with/ after prostate surgery, cardiovascular operations and liver transplants.There are data about effective rFVIIa usage in neurology and neurosurgery patients (intracranial haemorrhages, obstetrics and gynecology field. Possible future indications are thrombocytopenias, thrombocytopathias (Glanzmann

Vacuum magnetic field and modular coil system of the advanced stellarator Wendelstein VII-AS

International Nuclear Information System (INIS)

Rau, F.; Kisslinger, J.; Wobig, H.

1982-06-01

The vacuum field and the modular coils of the advanced stellarator WENDELSTEIN VII-AS are described. Each of the five field periods contains 9 different twisted coils, one of them with increased dimensions and current in order to provide sufficient access. The standard vacuum field configuration (B=3 T, t=0.39, aspect ratio approx. equal to 10, low shear, and magnetic well) can be varied by toroidal and vertical fields, or by changing independently the current in the large special coils. From a study of magnetic field perturbations some estimates are derived for the admissible coil tolerances. (orig.)

Stabilization of the (2,1) tearing mode and of the current disruption in the W VII-A stellarator

International Nuclear Information System (INIS)

Bartlett, D.V.; Cannici, G.; Cattanei, G.

1980-01-01

A numerical code based on a Δ'-analysis is applied to calculate the saturated amplitude of tearing modes dependent on the current density profile. The only stellarator effect included is the additional, shearless external rotational transform in the safety factor profile q(r). In this way, the stellarator field shifts the resonant q=2 surface toward the outside, where the current density gradient is smaller, and stabilizes the (2,1) mode as observed experimentally. Also the measured dependence of the (2,1) mode amplitude on electron density and plasma current can be absolutely predicted by the calculations. - In addition to stabilizing the (2,1) tearing mode, the current disruption is suppressed in Ohmically heated W VII-A discharges for approximately >0.15. The experimental findings, together with the calculated island widths, are compared with the predictions of a theoretical model proposed by several authors to explain the current disruption. (author)

Evolution of radiation losses and importance of charge exchange between plasma impurities and injection beam neutrals in the W VII-A stellarator

International Nuclear Information System (INIS)

Smeulders, P.

1981-01-01

In certain discharges during Neutral Injection (N.I.) (84 0 CO-injection) in the 1 = 2, m = 5 WENDELSTEIN VII-A Stellarator impurity accumulation in the plasma center seems to occur as seen by bolometric, spectroscopic and ultra soft X-ray (USX) measurement. The time evolution of the radiation losses is shown. Three possible sources of the impurities which are responsible for the high central radiation losses are: - Beam injected impurities. - Plasma wall interaction. - Molybdenum protection plates. Possible mechanisms that can be responsible for the central impurity accumulations are: - An inward flow of the plasma or beam impurities. - An increased peaking of the depostion of the beam impurities. Various factors influencing the behaviour of the central radiation are mentioned. (orig./AH)

Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

Science.gov (United States)

Weil, D; Levy, G; Sahly, I; Levi-Acobas, F; Blanchard, S; El-Amraoui, A; Crozet, F; Philippe, H; Abitbol, M; Petit, C

1996-04-16

The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells

OpenAIRE

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-01-01

Background: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian ca...

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11)

NARCIS (Netherlands)

Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

2004-01-01

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).

NARCIS (Netherlands)

Luijendijk, M.W.J.; Wijk, E. van; Bischoff, A.M.L.C.; Krieger, E.; Huygen, P.L.M.; Pennings, R.J.E.; Brunner, H.G.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, J.M.J.

2004-01-01

Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C

OpenAIRE

Sánchez Rodríguez, Yoan Antonio; Arús Soler, Enrique; López Saura, Pedro; Nodarse Cuní, Hugo

2011-01-01

INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales...

Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

International Nuclear Information System (INIS)

Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

1984-01-01

The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble 3 H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl 2 (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of 3 H preceded the appearance of Factor IXa activity, and the percentage of 3 H released remained constant when the mole fraction of 3 H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of 3 H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant

Life, limb or off-label recombinant VIIa use in the setting of limited blood assets: a case study.

Science.gov (United States)

Carr, Marcus E; Vickaryous, Brian

2013-06-01

Due to the lack of adequate controlled trials, the off-label use of recombinant factor VIIa (rFVIIa) to control hemorrhage in trauma patients remains controversial. The decision regarding when to initiate rFVIIa therapy is particularly problematic. Whereas most reports and trials have delayed use until significant bleeding has occurred, there is some evidence that coagulopathy develops early in some trauma patients, raising the possibility that early rFVIIa use may be more clinically efficacious. Herein, we report the case of a hemodynamically unstable patient with massive blood loss from multiple gunshot wounds and who had a potentially salvageable upper extremity. Rapid hemorrhage despite efforts to surgically control the bleeding resulted in virtual exhaustion of the facilities' limited blood component supply. Hemorrhage was controlled when rFVIIa was added to hypotensive resuscitation allowing salvage of the arm and significant conservation of blood products. This case raises the question as to whether earlier off-label use of this agent should be considered when amputation for hemorrhage control is being considered and/or conservation of limited blood assets is needed.

A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

Science.gov (United States)

Mehta, Darshan A; Oladapo, Abiola O; Epstein, Joshua D; Novack, Aaron R; Neufeld, Ellis J; Hay, Joel W

2016-02-01

Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to

Vírus influenza recombinantes como vetores vacinais: desenvolvimento e aplicação no modelo de doença de chagas

OpenAIRE

Rafael Polidoro Alves Barbosa

2014-01-01

As vacinas são consideradas uma das aplicações médicas mais bem sucedidas e eficazes na prevenção de doenças infecciosas. Há estimativas que até 3 milhões de vidas são salvas através de vacinação por ano, além de cem milhões de pessoas que deixam de ficar doentes reduzindo o impacto econômico e social causado por diversas doenças. Dentre as tecnologias mais viáveis para o desenvolvimento de novas vacinas se encontram os vírus recombinantes. Em 2010, nosso grupo demonstrou a viabilidade da con...

Ala397Asp mutation of myosin VIIA gene segregating in a Spanish family with type-Ib Usher syndrome.

Science.gov (United States)

Espinós, C; Millán, J M; Sánchez, F; Beneyto, M; Nájera, C

1998-06-01

In the current study, 12 Spanish families affected by type-I Usher syndrome, that was previously linked to chromosome 11q, were screened for the presence of mutations in the N-terminal coding portion of the motor domain of the myosin VIIA gene by single-strand conformation polymorphism analysis of the first 14 exons. A mutation (Ala397Asp) segregating with the disease was identified, and several polymorphisms were also detected. It is presumed that the other USHIB mutations in these families could be located in the unscreened regions of the gene.

Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

NARCIS (Netherlands)

Ree, M.A. van de; Maat, M.P. de; Kluft, C.; Meinders, A.E.; Princen, H.M.; Huisman, M.V.

2003-01-01

BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive

Obtención de anticuerpos monoclonales de ratón contra proteasa de cisteína 5 recombinante de Entamoeba histolytica

Directory of Open Access Journals (Sweden)

Juanita Trejos S.

2012-08-01

Full Text Available Objetivo. Obtener anticuerpos monoclonales de ratón contra la proteasas de cisteína 5 (EhCP5 de Entamoeba histolytica. Materiales y métodos. Se inmunizaron ratones BALB/c por vía intraperitoneal con adyuvante de Freund completo e incompleto con la proteína recombinante EhCP5 obtenida a partir del cultivo de E.coli DH5α trasfectada con el vector recombinante pJC45 que expresa dicha proteína. Se seleccionó el animal con mejor respuesta de anticuerpos. Al cual se le extrajo su bazo como fuente de linfocitos B, los cuales se fusionaron utilizando PEG con células de mieloma de ratón SP2-0/Ag14. Se procedió a selección de los hibridomas y a la evaluación de los sobrenadantes de las colonias que crecieron a los 7 días mediante ELISA. Los hibridomas con valores más altos de anticuerpos específicos contra la proteína EhCP5r se seleccionaron, y los clones obtenidos por diluciones limitantes fueron expandidos. Resultados. A partir de un clon secretor estable se purifico el anticuerpo monoclonal anti EhCP5r del isotipo IgG1 por cromatografía de afinidad con proteína G. Los clones fueron expandidos in vivo e in vitro. Con el anticuerpo purificado se diseñaron tres sistemas de captura para evaluar la aplicabilidad del anticuerpo monoclonal anti EhCP5r como método inmunodiagnóstico. Conclusiones. Se logro la producción de un anticuerpo monoclonal específico contra EhCP5r que permite diferenciar Entamoeba histolytica de Entamoeba dispar.

Klassiõpetaja peab särama / Ly Melesk, Kairis Kontus, Leida Talts, Viia Hang...[jt.] ; küsitles Anu Mõttus

Index Scriptorium Estoniae

2007-01-01

Vestlusringis on Tallinna Kuristiku Gümnaasiumi klassiõpetajad Viia Hang ja Ly Melesk, Tallinna Ülikooli 5. kursuse üliõpilane ja Tallinna Lepistiku Lasteaed-Algkooli õpetaja Kairis Kontus, Tallinna Ülikooli algõpetuse õppetooli juhataja Leida Talts ning algõpetuse õppetooli pedagoogika ja algõpetuse metoodika õppejõud Mare Müürsepp. Kui hästi on Tallinna Ülikool ja tema eelkäijad suutnud algklassiõpetajaid ette valmistada ja mis neil igapäevatöös toime tulla aitab

Is prophylaxis required for delivery in women with factor VII deficiency?

Science.gov (United States)

Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

2013-11-01

Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

Obtención y evaluación preliminar de un virus canarypox recombinante como candidato a vacuna antirrábica Development and preliminary assessment of a recombinant canarypox virus as an antirabic vaccine candidate

Directory of Open Access Journals (Sweden)

Flavia Zanetti

2012-06-01

Full Text Available En la Argentina, la rabia está circunscripta a algunas provincias del norte. La disponibilidad de nuevas vacunas que eliminen la manipulación del virus rábico y que permitan el control de la enfermedad es de importancia estratégica nacional y regional. Las vacunas basadas en poxvirus recombinantes se han utilizado con éxito como vacunas antirrábicas a nivel mundial. SI bien estos sistemas no están disponibles comercialmente, la plataforma de obtención de virus canarypox (CNPV recombinantes ya ha sido implementada en nuestro laboratorio. El objetivo de este trabajo fue obtener y evaluar un candidato a vacuna antirrábica basado en CNPV recombinantes que expresan la glicoproteína G (RG del virus rábico (RV. Se construyó un virus recombinante que expresa la secuencia codificante de RG (CNPV-RG. La inoculación de ratones con este virus indujo altos títulos de anticuerpos seroneutralizantes de RV (3,58 y 9,76 Ul/ml después de una o dos inmunizaciones, respectivamente y protegió al 78 % de los animales desafiados intracerebralmente con RV. Además, se determinó que el CNPV-RG posee una potencia relativa de 3,5 Ul/ml. Los resultados obtenidos constituyen la primera etapa en la evaluación del CNPV-RG como candidato a vacuna antirrábica. Se requerirán nuevos ensayos para confirmar su utilidad en especies de interés veterinario.In Argentina, rabies is limited to some northern provinces. Availability of new vaccines abolishing the handling of the rabies virus and allowing disease control has regional and national strategic importance. Vaccines based on recombinant poxviruses have been successfully used as antirabic vaccines worldwide. Although these systems are not commercially available, the platform to obtain recombinant canarypox viruses (CNPV has been previously set up in our laboratory. The aim of this work was the development and evaluation of an antirabic vaccine candidate based on recombinant CNPV expressing the rabies virus (RV

Expresión y sororreactividad de la lipoproteína recombinante de 43-kda de Bartonella bacilliformis

Directory of Open Access Journals (Sweden)

Carlos Padilla R

2006-07-01

Full Text Available Objetivo: La lipoproteína de 43-kDa de Bartonella bacilliformis fue obtenida en su forma recombinante (rBbLppB y purificada para evaluar su serorreactividad mediante ELISA. Materiales y métodos: Los niveles de anticuerpos IgG e IgM humanos en los sueros de pacientes con Bartonelosis confirmada y sueros de otras enfermedades (salmonelosis, Brucelosis y leptospirosis frente a rBbLppB fueron evaluados por ELISA, se utilizó sueros de personas sanas como controles. Resultados: La sensibilidad y la especificidad del ELISA IgG fueron 70,4% y 90% respectivamente. Asimismo, la sensibilidad y especificidad de ELISA IgM fueron 85,2% y 90% respectivamente. Conclusiones: Estos resultados demuestran que el ELISA usando rBbLppB tiene una buena sensibilidad y especificidad y puede ser considerada como un buen antígeno para el diagnóstico de Bartonelosis causada por B. bacilliformis.

Reflectometry observations of density fluctuations in Wendelstein VII-AS stellarator

International Nuclear Information System (INIS)

Sanchez, J.; Hartfuss, H.J.; Anabitarte, E.; Navarro, A.P.

1991-01-01

In the almost shearless stellarator Wendelstein VII-AS strong correlation between the confinement properties and the rotational transform iota has been found. Reduced confinement was observed for the low order rational values 1/2 and 1/3. In their vicinity best confinement is observed. In general optimum confinement is obtained in the low shear configuration if the 'resonant' iota values can be excluded from the plasma column. The iota profile inside the plasma is affected by toroidal currents and beta effects. Although the global net current can be kept at zero level using a small OH induced current opposed to the gradient driven bootstrap current, the different currents flow at different radial positions affecting the iota profile. Tools for configuration control inside the plasma are besides OH current vertical fields and the currents driven by the NBI and most promising the ECH heating systems. In this context experimental information on the iota profile is highly needed. The localization of rational surfaces by reflectometry seems possible. Radially resolved density fluctuation measurements have been carried out by means of a simple microwave reflectometry system. The method is based on the reflection of microwave radiation in the millimeter range at the plasma cutoff layer. (orig./AH)

Impurity transport in the Wendelstein VII-A stellarator

International Nuclear Information System (INIS)

1985-01-01

Impurity radiation losses in net-current-free neutral-beam-heated plasmas in the Wendelstein W VII-A stellarator are the combined effect of particularly strong impurity sources and improved particle confinement as compared with ohmically heated tokamak-like plasma discharges. Experiments are described and conclusions are drawn about the impurity species, their origin and their transport behaviour. The impurity transport is modelled by a 1-D impurity transport and radiation code. The evolution of the total radiation in time and space deduced from soft-X-ray and bolometer measurements can be fairly well simulated by the code. Experimentally, oxygen was found to make the main contribution to the radiation losses. In the calculations, an influx of cold oxygen desorbed from the walls of the order of 10 13 -10 14 cm -2 .s -1 and a rate of fast injected oxygen corresponding to a 1% impurity content of the neutral beams in combination with neoclassical impurity transport leads to quantitative agreement between the simulation and the observed radiation. The transport of A1 trace impurities injected by the laser blow-off technique was experimentally studied by soft-X-ray measurements using a differential method allowing extraction of the time evolution of A1 XII, XIII radial profiles. These are compared with code predictions, together with additional spectroscopic measurements. The main features of the impurity transport are consistent with neoclassical predictions, which explain particularly the central impurity accumulation. Some details, however, seem to require additional 'anomalous' transport. Such an enhancement is correlated with distortions of the magnetic configuration around resonant magnetic surfaces. (author)

Recombinant Activated Factor VIIa (rFVIIa) Treatment in Very-Low-Birth-Weight (VLBW) Premature Infants with Acute Pulmonary Hemorrhage: A Single-Center, Retrospective Study.

Science.gov (United States)

Cosar, Hese; Isik, Halil; Cakır, Salih Cagrı; Yar, Nese; Goksen, Bulent; Tokbay, Hakan; Kertmen, Hasan; Erdoğan, Nihal; Durak, Ikbal

2017-02-01

We aimed to evaluate the efficacy of intravenous administration of recombinant activated factor VIIa (rFVIIa) for acute pulmonary hemorrhage treatment in very-low-birth-weight (VLBW) premature infants. This study was carried out retrospectively in premature infants with pulmonary hemorrhage that were ≤30 weeks gestational age or hemorrhage who were hospitalized in our neonatal intensive care unit between 01 January 2013 and 31 December 2015 were evaluated. Group 1 (n = 21) received rFVIIa support within the first 30 min of pulmonary hemorrhage plus conventional treatment, while Group 2 (n = 21) received conventional treatment only. The number of patients whose pulmonary hemorrhage was stopped within the first 2 h was significantly higher in Group 1 than Group 2 (n = 14 vs n = 4; p = 0.002). After pulmonary hemorrhage, hemoglobin values of Group 1 were higher than Group 2 (11.12 ± 1.06 vs 10.14 ± 1.59 g/dL; p = 0.024). Erythrocyte suspension (1.43 ± 4.51 vs 5.71 ± 7.46 mL/kg; p = 0.030) and fresh frozen plasma use (5.71 ± 8.10 vs 19.52 ± 12.44 mL/kg; p hemorrhage after 72 h, overall mortality, mortality from pulmonary hemorrhage, surfactant use, intubation time, hospitalization duration, intraventricular hemorrhage (IVH), severe IVH, patent ductus arteriosus rates, or short-term complication rates. rFVIIa administration was observed to be effective in stopping pulmonary hemorrhage, reducing blood product requirement, and improving coagulation test parameters. Prospective studies are needed to evaluate the efficacy, reliability, and long-term results of rFVIIa in the prevention and treatment of pulmonary hemorrhage in premature infants.

Activity of recombinant factor VIIa under different conditions in vitro

DEFF Research Database (Denmark)

Bladbjerg, Else-Marie; Jespersen, Jørgen

2008-01-01

Recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Måløv, Denmark) is an effective drug for treatment of bleeding in patients with haemophilia A or B and inhibitors. Little is known about physiological conditions influencing the efficacy of recombinant activated factor VII. We...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30......, 33, 37, and 40 degrees C, or diluted 0, 10, 20, 40, and 60% with dextran before analysis. Samples were analysed as rotational thromboelastometry in whole blood (clotting time, clot formation time, and maximum clot firmness) with and without Innovin (tissue factor), and as factor VII coagulant...

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

Science.gov (United States)

Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

1998-04-15

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

ECRH experiments on the W VII-A stellarator

International Nuclear Information System (INIS)

Whilelm, R.; Erckmann, V.; Janzen, G.; Mueller, G.; Schueller, P. G.; Schwoerer, K.; Thumm, H.

1985-01-01

Plasma build-up and heating of a ''currentless'' plasma by means of ECR wave irradiation were studied at the Garching W VII-A stellarator. The experiments were performed at 28 GHz with approx. 200 kW RF power and a pulse duration 02 mode corresponding to a 50% O-mode and 50% X-mode mixture) was launched directly into the plasma from the low field side. In a second step the radiation was converted into the almost linearly polarized TE 11 mode and irradiated in O-mode orientation (E-tilde parallel to B-barsub(o), k-bar perpendicular to B-barsub(o)) into the torus, the nonabsorbed part of the RF power was reflected into the plasma in the X-mode by a focussing polarization twist reflector mounted to the inner torus wall. As a main result the heating efficiency has been slightly improved by the transition from ''simple'' to ''advanced'' wave launching (up to 50% instead of approx. 40%). The central electron temperatures were remarkably increased from approx. 700 eV to 1200 eV due to the well localized O-mode absorption of the TE 11 beam, however. The X-mode from the mirror on the other hand does not contribute to the total plasma energy as expected. This is explained by a local absorption of the arising Bernstein waves due to a macroscopically turbulent behaviour of the plasma in the outer regions. Possibly as a result of wave decay into lower hybrid waves pronounced ion tail heating was observed. For both kinds of wave irradiation toroidal plasma currents were generated. This seems to be caused by asimmetrically confined co- and counter-streaming fast electrons

Evaluación serológica de una proteína recombinante a partir de una cepa aislada del virus de la fiebre amarilla en el Perú: un estudio piloto

Directory of Open Access Journals (Sweden)

Carlos Yábar V

2003-10-01

Full Text Available Objetivo: Evaluar serológicamente una proteína recombinante de 66 kDa (Er66 de una cepa del virus de la fiebre amarilla aislada en el Perú usando anticuerpos inmunoreactivos. Material y métodos: La proteína Er66 fue expresada in vitro en la bacteria Escherichia coli y enfrentada a títulos de 1/100, 1/50 y 1/25 de anticuerpos monoclonales, y a sueros con anticuerpos IgM e IgG inmunoreactivos contra el virus de la fiebre amarilla mediante ensayos de Western blot (WB. Asimismo, se evaluaron proteínas totales de las cepas de referencia del virus dengue (DEN y fiebre amarilla como controles de antigenicidad. Resultados: La proteína recombinante Er66 presentó antigenicidad contra títulos de 1/50 y 1/25 de anticuerpo monoclonal (MAB8701; sin embargo, no se observó inmunoreactividad en sueros positivos para fiebre amarilla y dengue. Los ensayos con extractos crudos de la cepa de fiebre amarilla Asibi 17D (PTFA revelaron que la antigenicidad de las proteínas virales comprendidas entre 60 y 80 kDa fue afectada negativamente a temperaturas desnaturalizantes de 100°C. En cambio, tratamientos con ß-mercaptoetanol sin calor generó un aumento de la antigenicidad de dichas proteínas. Siguiendo este mismo principio, la proteína Er66 fue sometida a tratamientos desnaturalizantes con ß-mercaptoetanol sin incluir calor y fue enfrentada nuevamente a los sueros reactivos. El resultado final reveló que la proteína Er66 generó inmunoreactividad frente a sueros con altos títulos de anticuerpos IgM e IgG para fiebre amarilla mientras que en otras muestras se observó una débil señal. Conclusiones: Los datos obtenidos en este trabajo demuestran que la Er66 pudo ser reconocida por anticuerpos IgM e IgG específicos para fiebre amarilla presentes en sueros de pacientes infectados. Los datos presentados en este artículo sugieren el uso de proteínas recombinantes como posibles candidatas de valor diagnóstico para la FA.

Algunas variables clínicas y de laboratorio en pacientes adultos con leucemia mieloide crónica tratados con interferón alfa recombinante + citosina arabinósido

OpenAIRE

Espinosa Martínez, Edgardo; Díaz Durán, Carmen Virginia; Ávila Cabrera, Onel; Hernández Padrón, Carlos; Rodríguez, Luis Ramón; Izquierdo Cano, Lisset; Amor Vigil, Ana María; Lavaut Sánchez, Kalia; Espinosa Estrada, Edgardo; Wade Mateo, Maura; Estrada del Cueto, Marianela

2011-01-01

La leucemia mieloide crónica del adulto es la hemopatía maligna más frecuente dentro de los síndromes mieloproliferativos. En un estudio retrospectivo longitudinal realizado entre enero de 1985 y diciembre de 2009, se evaluaron 46 pacientes en fase crónica atendidos en el Instituto de Hematología e Inmunología. Todos recibieron tratamiento inicial citorreductor y posteriormente interferón ? recombinante (INF?r) + citosina arabinósido. El 41,0 % de los enfermos presentó un índice pronóstico de...

Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.

Science.gov (United States)

Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Wenyue; Yang, Jun

2016-05-01

Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin.

Identification and biochemical analysis of Slac2-c/MyRIP as a Rab27A-, myosin Va/VIIa-, and actin-binding protein.

Science.gov (United States)

Kuroda, Taruho S; Fukuda, Mitsunori

2005-01-01

Slac2-c/MyRIP is a specific Rab27A-binding protein that contains an N-terminal synaptotagmin-like protein (Slp) homology domain (SHD, a newly identified GTP-Rab27A-binding motif), but in contrast to the Slp family proteins, it lacks C-terminal tandem C2 domains. In vitro Slac2-c simultaneously directly interacts with both Rab27A and an actin-based motor protein, myosin Va, via its N-terminal SHD and middle region, respectively, consistent with the fact that the overall structure of Slac2-c is similar to that of Slac2-a/melanophilin, a linker protein between Rab27A and myosin Va in the melanosome transport in melanocytes. Unlike Slac2-a, however, the middle region of Slac2-c interacts with two types of myosins, myosin Va and myosin VIIa. In addition, the most C-terminal part of both Slac2-a and Slac2-c functions as an actin-binding domain: it directly interacts with globular and fibrous actin in vitro, and the actin-binding domain of Slac2-a and Slac2-c colocalizes with actin filaments when it is expressed in living cells (i.e., PC12 cells and mouse melanocytes). In this chapter we describe the methods that have been used to analyze the protein-protein interactions of Slac2-c, specifically with Rab27A, myosin Va/VIIa, and actin.

Vectores recombinantes basados en el virus modificado de ankara (MVA), con deleción en el gen C6L, como vacunas contra el VIH/SIDA y otras enfermedades

OpenAIRE

García-Arriaza, J.; Gómez, Carmen E.; Esteban, Mariano

2011-01-01

[ES] La presente invención engloba dentro de los campos de la biología molecular y de la biotecnología. Especificamente se refiere a virus recombinantes basados en el virus modificado de Ankara (MVA) que expresan los antigenos gp120 y Gag-Pol-Nef del virus de la inmunodeficienciahumana (VIH-1) de subtipo B (MVA-B), sobre los que see ha delecionado el gen de vaccinia C6L, y que han sido diseñados para utilizarse como vacunas contra el VIH/SIDA y otras enfermedades.

Vectores recombinantes basados en el virus modificado de Ankara (MVA), con deleción en el gen C6L, como vacunas contra el VIH/SIDA y otras enfermedades

OpenAIRE

García-Arriaza, J.; Gómez, Carmen E.; Esteban, Mariano

2011-01-01

La presente invención se engloba dentro de los campos de la biología molecular y de la biotecnología. Específicamente se refiere a virus recombinantes basados en el virus modificado de Ankara (MVA) que expresan los antígenos gp120 y Gag-Pol-Nef del virus de la inmunodeficiencia humana (VIH-1) de subtipo B (MVA-B), sobre los que se ha delecionado el gen de vaccinia C6L, y que han sido diseñados para utilizarse como vacunas contra el VIH/SIDA y otras enfermedades.

Clinical Outcomes of a Pharmacy-Led Blood Factor Stewardship Program.

Science.gov (United States)

Trueg, Anne O; Lowe, Christopher; Kiel, Patrick J

To report the results of a pharmacist-directed blood factor stewardship program targeting off-label utilization designed to limit use to established organizational guidelines in high-risk populations. Prospective evaluation of recombinant factor VIIa and prothrombin complex concentrate orders beginning June 2013 through May 2014 and a matched retrospective cohort from June 2012 to May 2013. Matched cohorts were evaluated for 28-day mortality, change in international normalized ratio (INR), adverse events, concurrent blood product use, and cost savings. Forty-two orders for blood factor were ordered between June 2013 and May 2014, 70 orders in the year before (N = 112). Twenty eight-day mortality was not different between the cohorts: 53.9% versus 50% (P = 0.77). Blood factor use with underlying liver failure and active bleeding was strongly associated with 28-day mortality: odds ratio (95% confidence interval), 2.9 (1.5-7.14) and 2.91 (0.01-2.91), respectively. Blood products dispensed increased over the year with plasma products the most significant (1 vs. 4 P = 0.004). All other clinical outcomes were nonsignificant. An annual cost savings of $375,539 was achieved, primarily through a significant reduction in recombinant factor VIIa and avoidance in high-risk patients. Use of off-label blood factors can be controlled through a pharmacist-led stewardship program. Twenty eight-day mortality was not different between the 2 cohorts; however, identification of risk factors for death associated with blood factor use allows for restriction in high-risk populations, creates a discussion of futile care, and yields cost savings.

Tumor Angiogenesis Therapy Using Targeted Delivery of Paclitaxel to the Vasculature of Breast Cancer Metastases

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Shijun Zhu

2014-01-01

Full Text Available Breast cancer aberrantly expresses tissue factor (TF in cancer tissues and cancer vascular endothelial cells (VECs. TF plays a central role in cancer angiogenesis, growth, and metastasis and, as such, is a target for therapy and drug delivery. TF is the cognate receptor of factor VIIa (fVIIa. We have coupled PTX (paclitaxel, also named Taxol with a tripeptide, phenylalanine-phenylalanine-arginine chloromethyl ketone (FFRck and conjugated it with fVIIa. The key aim of the work is to evaluate the antiangiogenic effects of PTX-FFRck-fVIIa against a PTX-resistant breast cancer cell line. Matrigel mixed with VEGF and MDA-231 was injected subcutaneously into the flank of athymic nude mice. Animals were treated by tail vein injection of the PTX-FFRck-fVIIa conjugate, unconjugated PTX, or PBS. The PTX-FFRck-fVIIa conjugate significantly reduces microvessel density in matrigel (p<0.01–0.05 compared to PBS and unconjugated PTX. The breast cancer lung metastasis model in athymic nude mice was developed by intravenous injection of MDA-231 cells expressing luciferase. Animals were similarly treated intravenously with the PTX-FFRck-fVIIa conjugate or PBS. The conjugate significantly inhibits lung metastasis as compared to the control, highlighting its potential to antagonize angiogenesis in metastatic carcinoma. In conclusion, PTX conjugated to fVIIa is a promising therapeutic approach for improving selective drug delivery and inhibiting angiogenesis.

Isolation of recombinant strains with enhanced pectinase production by protoplast fusion between Penicillium expansum and Penicillium griseoroseum Isolamento de linhagens recombinantes com maior produção de pectinases por meio de fusão de protoplastos entre Penicillium expansum e Penicillium griseoroseum

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Maurilio Antonio Varavallo

2007-03-01

Full Text Available Protoplast fusion between complementary auxotrophic and morphological mutant strains of Penicillium griseoroseum and P. expansum was induced by polyethylene glycol and calcium ions (Ca2+. Fusant strains were obtained in minimal medium and a prototrophic strain, possibly diploid, was chosen for haplodization with the fungicide benomyl. Different recombinant strains were isolated and characterized for occurrence of auxotrophic mutations and pectinolytic enzyme production. The fusant prototrophic did not present higher pectinase production than the parental strains, but among 29 recombinants analyzed, four presented enhanced enzyme activities. The recombinant RGE27, which possesses the same auxotrophic and morphologic mutations as the P. griseoroseum parental strain, presented a considerable increase in polygalacturonase (3-fold and pectin lyase production (1.2-fold.Fusões de protoplastos entre linhagens mutantes auxotróficas e morfológicas complementares de Penicillium griseoroseum e P. expansum foram induzidas por polietilenoglicol e íons cálcio (Ca2+. Fusionantes foram obtidos em meio mínimo e uma linhagem prototrófica, possivelmente diplóide, foi selecionada para a haploidização com o fungicida benomil. Diferentes linhagens recombinantes foram isoladas e caracterizadas quanto à presença de mutações auxotróficas e a produção de enzimas pectinolíticas. O fusionante prototrófico não apresentou maior atividade de pectinases em relação às linhagens parentais, entretanto, entre 29 recombinantes analisados, quatro apresentaram maiores atividades enzimáticas. O recombinante RGE27, o qual possui as mesmas mutações auxotróficas e morfológicas que a linhagem parental de P. griseoroseum, apresentou um aumento considerável na produção de poligalacturonase (3 vezes e de pectina liase (1,2 vezes.

Mode and sawtooth behaviour during neutral beam injection in the W VII-A stellarator

International Nuclear Information System (INIS)

Grieger, G.; Renner, H.; Sapper, J.; Wobig, H.; Dorst, D.; Cattanei, G.; Javel, P.; Rau, F.; Zippe, M.; Jaeckel, H.

1980-02-01

The mode behaviour during Neutral Beam Injection in the WENDELSTEIN VII-A stellarator is presented. The analysis is mainly relying on soft X-ray measurements. Two types of discharges were found during Neutral Beam Injection with plasma currents >= 20 kA. The first type is dominated by large, regular and long sawteeth, which are caused by a (m,n) = (1,1) mode. In the second type the sawteeth disappear completely. Later in the discharge a local disruption causes a transition to the first type; this disruption has a (3,2) mode precursor. A new mode (2,2) is found and phase coupled to the (3,2) mode. Even at a high external rotational transform (t 0 = 0.23) a large (2,1) mode is found after the (3,2) mode has caused the local disruption. At slightly lower external rotational transform values major current disruptions may even occur. This is mainly due to the enhanced edge heating by the Neutral Beam Injection. Results of simulations of the mode structures are also presendet. (orig./GG)

FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139

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Andrea Roxanne J. Anas

2017-08-01

Full Text Available The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 µM, which was more efficient than thrombin inhibition of EC50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.

Two Finnish USH1B patients with three novel mutations in myosin VIIA.

Science.gov (United States)

Vastinsalo, Hanna; Isosomppi, Juha; Aittakorpi, Anne; Sankila, Eeva-Marja

2006-09-21

Usher syndrome (USH) is an autosomal recessive disorder resulting in retinal degeneration and sensorineural deafness caused by mutations in at least 10 gene loci. USH is divided into three main clinical types: USH1 (33-44%), USH2 (56-67%), and USH3. Worldwide, USH1 and USH2 account for most of the Usher syndrome cases with rare occurrence of USH3. In Finland, however, USH3 is the most common type (40%), explained by genetic and geographical isolation accompanied with a founder mutation, while USH1 is estimated to comprise 34% and USH2 12% of all USH cases. We examined two unrelated Finnish USH1 patients by sequencing. We found three new myosin VIIA (MYO7A) mutations: p.K923AfsX8, p.Q1896X, and p.E1349K. The p.K923AfsX8 mutation was present in both patients as well as in one of 200 Finnish control chromosomes. This is the first molecular genetic study of USH1 in Finland. We have found three new pathological mutations causing either premature termination of translation or replacement of an evolutionary conserved MYO7A amino acid.

Reversal of coagulopathy in critically ill patients with traumatic brain injury: recombinant factor VIIa is more cost-effective than plasma.

Science.gov (United States)

Stein, Deborah M; Dutton, Richard P; Kramer, Mary E; Scalea, Thomas M

2009-01-01

Traumatic brain injury (TBI) is the leading cause of death and disability after trauma. Coagulopathy is common in this patient population and requires rapid reversal to allow for safe neurosurgical intervention and prevent worsening of the primary injury. Typically reversal of coagulopathy is accomplished with the use of plasma. Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) has become increasingly used "off-label" in patients with neurosurgical emergencies to rapidly reverse coagulopathy. We hypothesized that the use of rFVIIa in this patient population would prove to be cost-effective as well as demonstrate clinical benefit. The trauma registry at the R Adams Cowley Shock Trauma Center was used to identify all coagulopatic trauma patients admitted between January 2002 and December 2007 with relatively isolated TBI (head Abbreviated Injury Scale score of >or=4). The medical records of patients were reviewed and demographics, injury-specific data, medications administered, laboratory values, blood product utilization, neurosurgical procedures, length of stay (LOS), discharge disposition, and outcome data were abstracted. Patients who received rFVIIa for reversal of coagulopathy were compared against those who did not receive rFVIIa. t Tests were used to compare differences between continuous variables, and chi2 analysis was used to compare categorical variables. A p value of percentage of patients with head Abbreviated Injury Scale score of 5 injuries, patients who underwent neurosurgical procedures and patients with preinjury warfarin use. There was no difference in total charges between these groups (mean US $63,403 in the conventionally treated group vs. $66,086). When patients who required admission to the intensive care unit were analyzed (n = 110, 50% received rFVIIa), total mean charges and costs were significantly lower in the group that received rFVIIa (mean US $108,900 vs. $77,907). Hospital LOS, days of mechanical

Estreptoquinasa recombinante en pacientes con infarto agudo del miocardio. Cardiocentro de Camaguey, 2008

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Héctor Mariño Cano

2015-12-01

Full Text Available Se realizó un estudio descriptivo longitudinal, con el objetivo de valorar la eficacia de la utilización de la Estreptoquinasa Recombinante en pacientes con Infarto Agudo de Miocardio (IMA en el Cardiocentro del Hospital Provincial Docente “Manuel Ascunce Doménech” en la provincia de Camagüey, en el período comprendido de enero a diciembre del 2008. El universo estuvo constituido por 200 pacientes, a los que se les diagnosticó Infarto Agudo de Miocardio y la muestra quedó formada por 80 pacientes que recibieron tratamiento trombolítico, las historias clínicas de los pacientes fueron la principal fuente de obtención de la información, utilizando  las  siguientes  variables: resultados criterio de perfusión, evolución clínica, criterio de reacciones adversas y la influencia que ejerce el tiempo puerta-aguja,  así como los cuidados de enfermería. Al terminar se observó que  el criterio de repercusión de mayor incidencia fue el eléctrico; la mayor cantidad de pacientes tuvieron buena evolución clínica; la hipotensión fue la reacción adversa más frecuente; el tiempo de puerta-aguja  que más incidió  fue el menor, de 3h; a todos los pacientes diagnosticados con infarto, que recibieron tratamiento trombolítico, se les  brindaron  cuidados de enfermería.

Postprandial triglycerides and blood coagulation.

Science.gov (United States)

Silveira, A

2001-01-01

Most of our lifetime we spend in the postprandial state. Postprandial triglyceridemia may represent a procoagulant state involving disturbances of both blood coagulation and fibrinolysis, in particular due to elevation of the plasma levels of activated factor VII (VIIa) and plasminogen activator inhibitor (PAI-1). Therefore, disturbances of the hemostatic system might, at least partly, account for by the link between hypertriglyceridemia and coronary heart disease (CHD). Factor VIIa is the first enzyme of the blood coagulation system and serves a priming function for triggering of the clotting cascade. The coagulant activity of factor VII (VIIc, total activity of factor VII in plasma) was identified as an independent predictor of myocardial infarction in initially healthy middle-aged men, and particularly of fatal coronary events, and both serum cholesterol and triglyceride concentrations correlated positively with the VIIc level. Addition of fat to diet has been consistently shown to cause a rapid conversion of the factor VII zymogen into its active form (VIIa) whereas the concentration of total protein is unaffected. Postprandial activation of factor VII is dependent on lipolytic activity and it is mainly supported by large triglyceride-rich lipoprotein of the VLDL class. Studies in vivo with specific coagulation factor-deficient patients indicate that factor IX is essential for the postprandial activation of factor VII. The basal generation of thrombin seems to be unaffected by increased plasma levels of VIIa. However, since VIIa-tissue factor complex is responsible for the initiation of the coagulation cascade, increased generation of VIIa in the postprandial state would increase the potential for thrombin production in the event of plaque rupture. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of the plasminogen activators in the circulation and thereby the principal inhibitor of the fibrinolytic system. Postprandial

Producción de anticuerpos policlonales IgG contra la proteina iduronato-2-sulfato sulfatasa y desarrollo de un sistema de detección para IDS humana recombinante.

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Olga Peña

2005-06-01

Full Text Available Introducción. La enfermedad de Hunter es un trastorno lisosómico caracterizado por la deficiencia de la enzima iduronato-2-sulfato sulfatasa (IDS (EC 3.1.6.13. Esta enfermedad, al igual que muchos trastornos metabólicos, son patologías intratables mediante la terapéutica convencional; sin embargo, existe la posibilidad de ser tratada alternativamente mediante terapia génica o terapia de reemplazo enzimático. Objetivo. El Instituto de Errores Innatos del Metabolismo (IEIM ha desarrollado un sistema de expresión de sulfatasas para producir IDS humana recombinante (IDShr en Escherichia coli y Pichia pastoris, con resultados favorables. El objetivo principal de este trabajo fue desarrollar un sistema de detección de IDS humana recombinante. Materiales y métodos. Para el efecto, se inmunizaron con IDS comercial de TKT (Cambridge, MA dos conejos de raza Nueva Zelanda blanca y los anticuerpos purificados a partir del suero se utilizaron en el desarrollo de una técnica semicuantitativa por dot-blot. Diferentes muestras de extractos crudos de fermentaciones con P. pastoris y E. coli se procesaron con el fin de poder determinar la presencia de la enzima. Resultados. Se demostró que los anticuerpos eran específicos en el reconocimiento de la IDS sin presentar reactividad cruzada con proteínas contaminantes de los extractos crudos. Conclusión. Por consiguiente, los anticuerpos se podrán usar en el desarrollo de una técnica ELISA tipo sandwich como método de detección y cuantificación de la enzima y en procesos de purificación de la misma mediante cromatografía de afinidad.

Construção e caracterização de linhagens bacterianas Gram-negativas recombinantes com capacidade aumentada para biorremediar efluentes contaminados com mercúrio e arsênio.

OpenAIRE

Carolina Angélica da Silva Parada

2012-01-01

Este trabalho descreve a construção de plasmídeos para expressão e ancoragem de proteínas de alta afinidade a íons Hg2+ e As5+. Os genes merR e arsR de C. metallidurans foram inseridos no vetor que contém o sistema para expressão e ancoragem de proteínas heterólogas em bactérias Gram-negativas originando os plasmídeos pCM-Hg e pCM-As. MerR e ArsR foram produzidas sob comando do promotor pan. E. coli recombinantes apresentaram resistência 100% superior a Hg2+ e As5+. C. metallidurans/pCM-As ap...

Balance energético y capacidad gluconeogénica de vacas lecheras a pastoreo tratadas con una baja dosis de somatotropina recombinante bovina en el período de transición

OpenAIRE

JL Sánchez; CA Wagemann; C Strieder-Barboza; M Noro

2014-01-01

El objetivo del estudio fue determinar el efecto de la dosis baja (250 mg/vaca) de somatotropina recombinante bovina (rbST) en vacas lecheras a pastoreo en período de transición sobre los indicadores energético-proteínicos y capacidad gluconeogénica. Se realizaron 3 ensayos: Preparto, se utilizaron 10 vacas preparto, grupo bST (n = 5): dosis única de rbST el día (d) 26 preparto, y control (n = 5); se obtuvieron muestras de sangre y se registró la condición corporal (CC) cada 3 d desde el 26 d...

Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa

DEFF Research Database (Denmark)

Larsen, Katrine S; Østergaard, Henrik; Bjelke, Jais R

2007-01-01

The remarkably high specificity of the coagulation proteases towards macromolecular substrates is provided by numerous interactions involving the catalytic groove and remote exosites. For FVIIa [activated FVII (Factor VII)], the principal initiator of coagulation via the extrinsic pathway, several...... for FVIIa by marked changes in primary substrate specificity and decreased rates of antithrombin III inhibition. Interestingly, these changes do not necessarily coincide with an altered ability to activate Factor X, demonstrating that inhibitor and macromolecular substrate selectivity may be engineered...

Factores asociados a una respuesta inadecuada a la vacunación contra la hepatitis B en personal sanitario

OpenAIRE

Tolosa Martínez Natividad; Tenías Burillo José María; Pérez Bermúdez Brígido; Sanchis Álvarez Juan Bautista

1998-01-01

FUNDAMENTO: La vacuna recombinante contra la hepatitis B confiere inmunidad aproximadamente en el 95 % de los casos, pero existe un porcentaje que responde insuficientemente. El objetivo de este trabajo es evaluar los factores que se asocian con una inadecuada respuesta inmunitaria. MÉTODOS: Se trata de un estudio observacional y analítico en el que se sigue retrospectivamente una cohorte de sujetos vacunados frente al virus de la hepatitis B (VHB). Se recogieron las variables de interés del ...

Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

DEFF Research Database (Denmark)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

2016-01-01

Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

OpenAIRE

Yoan Antonio Sánchez Rodríguez; Enrique Arús Soler; Pedro López Saura; Hugo Nodarse Cuní

2011-01-01

INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales...

EFECTO DE LA DENSIDAD CELULAR Y LA MULTIPLICIDAD DE INFECCIÓN SOBRE LA PRODUCCIÓN DE BACULOVIRUS RECOMBINANTES EN CULTIVOS DE CÉLULAS DE INSECTO

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Cuitláhuac Chávez-Peña

2010-01-01

célula con CCI de 1 y 2 x106 cél/mL. Se siguieron las cinéticas de crecimiento de las células infectadas, la concentración de proteína total y de la proteína gp64 en el sobrenadante de los cultivos y los títulos virales al momento de la cosecha. Se encontró que una MDI de 0.1 ufp/cél y una concentración celular de 1x106 cél/mL resultaron en el mayor título viral, 3.8 ± 2 x108 ufp/mL. Los mayores títulos virales estuvieron acompañados por un menor crecimiento celular. Los resultados de este trabajo pueden ser utilizados para producir resguardos de baculovirus recombinantes con títulos virales altos y mejorar la eficiencia del proceso.

Immunogenicity and antigenicity of the recombinant EMA-1 protein of Theileria equi expressed in the yeast Pichia pastoris Imunogenicidade e antigenicidade da proteína recombinante EMA-1 de Theileria equi expressa em Pichia pastoris

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Leandro Q. Nizoli

2009-06-01

Full Text Available The equine piroplasmosis caused by Theileria equi is one of the most important parasitic diseases of the equine, causing damage to animal health and economic losses. In T. equi, 2 merozoite surface proteins, equi merozoite antigen EMA-1 and EMA-2, have been identified as the most immunodominant antigens. This suggests that these antigens might be used as immunobiological tools. The EMA-1 of Theileria equi was cloned and expressed in the yeast Pichia pastoris. The transformed yeast was grown at high cell density, expressing up to 389 mg.L-1 of recombinant protein. The protein was concentrated and detected in Dot blot. The recombinant product was antigenically similar to the native protein as determined using monoclonal antibodies, and polyclonal antibodies obtained from equines naturally infected with T. equi. The immunogenicity of rEMA-1 protein was demonstrated by IFAT using sera from recombinant-protein-immunized mice using aluminum hydroxide as adjuvant. All animals vaccinated with rEMA-1 developed a high specific antibody response. This results suggest that rEMA-1expressed in P. pastoris might be a strong candidate to be used as an antigen for immune diagnostics as well as a vaccine antigen.A piroplasmose equina causada por Theileria equi é uma das mais importantes doenças parasitárias de equídeos, causando danos a saúde animal e perdas econômicas. Em T. equi, 2 proteínas de superfície de merozoítos, equi merozoite antigen EMA-1 e EMA-2, têm sido identificadas como antígenos imunodominantes. Sugerindo que estes antígenos possam ser usados como produtos imunobiológicos. O gene EMA-1 de T. equi foi clonado e expressado na levedura Pichia pastoris. As leveduras transformadas foram cultivadas a altas densidades celulares expressando 389 mg.L-1 de proteína recombinante. A proteína foi concentrada e detectada em Dot blot. O produto recombinante foi antigenicamente similar à proteína nativa quando determinado usando anticorpo

Relationship between Inflammation markers, Coagulation Activation and Impaired Insulin Sensitivity in Obese Healthy Women

International Nuclear Information System (INIS)

Soliman, S.Et; Shousha, M.A.

2011-01-01

Obesity, insulin resistance syndrome, and atherosclerosis are closely linked phenomena, often connected with a chronic low grade inflammatory state and pro thrombotic hypo fibrinolytic condition. This study investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. The study included 36 healthy obese women (body mass index ≥ 30), with normal insulin sensitivity (NIS, n = 18) or impaired insulin sensitivity (IIS, n 18), and 10 non obese women (body mass index < 25).Impaired insulin sensitivity patients had significantly higher levels of high sensitivity C-reactive protein (hs-CRP), transforming growth factor -β1(TGF-β1), plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragments 1 + 2 (F1 + 2) compared with either control subjects or normal insulin sensitivity patients. On the other hand, NIS patients had higher hs-CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, hs-CRP, PAI-1; factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. These results document an in vivo relationship between insulin sensitivity and coagulation activation in obesity. Here we report that obesity is associated with higher TGF-β, PAI-1, prothrombin fragments 1 and 2 (F1 + 2), and activated factor VII (VIIa) plasma levels, and that insulin resistance exacerbates these alterations. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease

Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

Science.gov (United States)

Livnat, Tami; Zivelin, Ariella; Tamarin, Ilia; Guetta, Victor; Salomon, Ophira

2009-12-01

Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding. Levels of clotting factors as well as inhibitors to factors II, V, VII, VIII, IX, X and XI were defined. For detection of inhibitors to prothrombin crossed immunoelectrophoresis was used. IgG was purified by commercial protein A column. Thrombin generation was measured using a fluorometric assay in platelet-poor and platelet-rich plasma. Inhibitors toward the activity of factors V, VII, VIII, IX, X and XI were defined and also an inhibitor to prothrombin antigen. No thrombin generation was induced in the patient's plasma by recalcification even in the presence of recombinant factor VIIa or factor VIII inhibitor bypassing activity. In contrast, addition of platelets from either donor or patient or synthetic phospholipids normalized the thrombin generation. The thrombin generation model showed that the addition of platelets and no recombinant factor VIIa or factor VIII inhibitor bypassing activity would correct thrombin generation in vitro. On this basis, platelet concentrates were administered to a patient with bleeding caused by lupus anticoagulant and low clotting factors activity.

Tratamiento con eritropoyetina humana recombinante Human recombinant erythropoietin therapy

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Hugo Donato

2006-02-01

Full Text Available La eritropoyetina recombinante (rHuEPO se ha transformado en la citoquina más utilizada terapéuticamente en el mundo. Luego del éxito obtenido en pacientes con insuficiencia renal terminal, se pudo establecer la utilidad de la terapia con rHuEPO para mejorar otras anemias, incluso en pacientes pediátricos y neonatos. El tratamiento o la prevención de la anemia del prematuro mediante el uso de rHuEPO llevó a una significativa reducción en cantidad de transfusiones y en exposición a dadores. Aún debe establecerse una clara definición sobre cuáles niños prematuros deben recibir tratamiento rutinariamente. Otras indicaciones en período neonatal incluyen anemias hiporregenerativas y hemolíticas. La eficacia de la rHuEPO en niños mayores, con excepción de la insuficiencia renal crónica, no ha sido tan exhaustivamente evaluada como en adultos. Mientras que durante los últimos años se han realizado gran cantidad de estudios en adultos con anemia asociada al cáncer o a infección por HIV, permitiendo establecer conclusiones claras sobre su eficacia, sólo escasa cantidad de estudios con pequeño número de pacientes han sido realizados en niños. Hasta la fecha, los resultados sugieren que la terapia con rHuEPO en niños es tan útil como en adultos, pero la realización de estudios aleatorizados prospectivos incluyendo gran número de pacientes es esencial para alcanzar conclusiones definitivas. Los resultados de estudios dirigidos a evaluar la eficacia de la rHuEpo para mantener una dosis adecuada de ribavirina en pacientes en tratamiento por hepatitis C son alentadores. La utilización potencial de los efectos no hemopoyéticos de la rHuEPO en neonatos es un terreno novedoso y apasionante. El rol de la Epo como citoprotector para sistema nervioso central y mucosa intestinal está bajo investigación exhaustiva.Recombinant human erythropoietin (rHuEpo has become the most widely used cytokine in the world. Following the success of

Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate

DEFF Research Database (Denmark)

Sølbeck, Sacha; Nilsson, Caroline U; Engström, Martin

2014-01-01

OBJECTIVE: Dabigatran is a new oral direct thrombin inhibitor. No specific antidote exists in the event of hemorrhage, but prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies. Sonoclot is a bedside viscoelastic instrument for monitoring...... different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC...

Establecimiento de un material de referencia de trabajo para interleucina-2 recombinante

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Maribel Vega

2005-08-01

Full Text Available Resumen La interleucina-2 es una glicoproteína humana de 133 aminoácidos que resulta vital para obtener una respuesta inmunológica efectiva. En el Centro de Ingeniería Genética y Biotecnología ha podido obtenerse por vía recombinante a partir de una cepa de Escherichia coli. Para el control de la calidad de cada lote producido se hizo necesaria la elaboración de un material de referencia de trabajo. En esta publicación se describen los pasos seguidos en la obtención del lote candidato y la preparación del material de referencia como tal. Se demostró que el patrón de trabajo preparado es homogéneo para el uso en las técnicas analíticas de control de calidad de la interleucina-2 y se predijo una pérdida de actividad inferior al 5 % anual mediante un estudio de estabilidad acelerada. Se obtuvieron valores adecuados para la pureza del material de referencia, evaluada por electroforesis y para la actividad biológica, que se estableció con trazabilidad al material de referencia internacional para este producto.Establishment of a working reference material for recombinant interleukin-2 Interleukin-2 is a human glycoprotein with 133 aminoacids that is crucial for attaining an effective immunological reaction. In the Center of Genetic Engineering and Biotechnology this protein has been obtained as a recombinant product from Eschericia coli bacteria. For the quality control of every batch produced, it was necessary to establish a working reference material. In this paper we describe the steps taken to obtain a candidate batch and the preparation of the working material as such. It was proved that the working pattern obtained.is homogenous for its use in the analytical techniques of quality control of interleukin-2. A loss of activity lower than an annual 5 % was predicted by an accelerated stability study. Adequate values were attained for the purity of the reference material, evaluated by electrophoresis, and for the biological

Probing the Role of Loops & Domains in Regulating Coagulation Factor VIIa Allostery and Specificity

DEFF Research Database (Denmark)

Sørensen, Anders Bundgård

2016-01-01

The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo).......The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo)....

In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

Science.gov (United States)

Augustsson, Cecilia; Persson, Egon

2014-11-13

Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

Recombinant-activated factor VII in patients with uncontrolled bleeding: A retrospective observational analysis

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Said D Abuhasna

2012-01-01

Full Text Available Background: Factor VIIa (recombinant has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Objective: The primary objective of this study was to assess the safety and effectiveness of factor VIIa (recombinant on blood transfusion requirements and coagulation parameters when used in patients whose bleeding was uncorrected by other means. The pharmacoeconomic impact for any discrepancy from our protocol was evaluated. Secondary outcomes included 4-hour and 28-day mortality, as well as safety of this agent in terms of thromboembolic complications. Materials and Methods: We retrospectively evaluated patients who received recombinant-activated factor VII (rFVIIa for uncontrolled bleeding from June 2008 to April 2011. The medical records of 33 patients were evaluated. Coagulation parameters and blood products were determined 24 hours before and 24 hours after administration of rFVIIa, and the results compared. Patients were also screened for any thromboembolic complications. Results: Administration of rFVIIa reduced blood transfusion requirements and improved coagulation parameters significantly (P<0.05. No thromboembolic complications were reported. Most of the dosing was consistent with those recommended in our institutional protocol, with discrepancies resulting in an average cost of $56 058. Moreover, pH was reported in only 67% of patients. All patients treated with rFVIIa survived up to 4 hours after receiving this agent, while the 28-day mortality was 24% (8/33. Conclusion: The use of rFVIIa appears to be safe and effective in promoting hemostasis, as evident from reducing transfusion requirements and improving the coagulation variables.

PENERAPAN MODEL PEMBELAJARAN NUMBER HEADS TOGETHER (NHT UNTUK MENINGKATKAN HASIL BELAJAR SISWA KELAS VIIA SMP NEGERI 2 TUNTANG PADA MATERI SEGITIGA

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Era Destiyandani

2016-12-01

Full Text Available Penelitian tindakan kelas ini bertujuan untuk meningkatkan hasil belajar dan mendeskripsikan kondisi siswa kelas VIIA SMP Negeri 2 Tuntang pada materi segitiga melalui penerapan model pembelajaran Number Heads Together (NHT. Melalui model pembelajaran NHT, tugas diberikan kepada semua siswa dimana siswa telah diberi nomor berbeda didalam kelompoknya namun masing-masing kelompok menggunakan penomoran yang sama. Pemanggilan nomor siswa secara acak untuk melaporkan hasil diskusi kelompok mendorong setiap siswa secara individu bertanggung jawab atas hasil belajarnya. Instrumen penelitian yang digunakan untuk mengambil data penelitian adalah soal tes dan lembar observasi. Penelitian ini diterapkan pada 31 siswa sebagai subjek dan menggunakan model spiral Kemmis dan McTaggart. Hasil penelitian menunjukkan bahwa persentase ketuntasan siswa untuk materi segitiga tentang mengidentifikasi sifat-sifat segitiga berdasarkan sisi dan sudutnya pada siklus I mencapai 87,1% tuntas dan ketuntasan meningkat menjadi 96,77% pada siklus II dengan materi pembelajaran menghitung keliling dan luas segitiga. Hasil ini menunjukkan bahwa penggunaan model pembelajaran NHT telah meningkatkan penguasaan materi segitiga oleh siswa.

Diagnóstico de ABPA em pacientes portadores de fibrose cística: utilidade clínica da pesquisa de IgE específica contra alérgenos recombinantes do Aspergillus fumigatus ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens

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Marina B. Almeida

2006-06-01

Full Text Available OBJETIVO: A aspergilose broncopulmonar alérgica (ABPA é um fator complicador da fibrose cística que pode determinar uma combinação devastadora na evolução da doença pulmonar. A sobreposição de sinais e sintomas das duas enfermidades dificulta o diagnóstico, mesmo aplicando critérios padronizados. O objetivo deste trabalho foi identificar, em grupo de portadores de fibrose cística, os casos de ABPA através da detecção de IgE específica contra os alérgenos recombinantes do Aspergillus fumigatus e confrontar esse método com os critérios preconizados pela Cystic Fibrosis Foundation. MÉTODOS: Cinqüenta e quatro pacientes de 2 a 20 anos, com características que poderiam estar isoladamente presentes na ABPA, foram avaliados sistematicamente, incluindo: dados clínicos, tomografia computadorizada de tórax, teste cutâneo de hipersensibilidade imediata para A. fumigatus; dosagem de IgE sérica total, RAST para A. fumigatus, e IgE sérica específica para alérgenos recombinantes r Asp f1, f2, f3, f4 e f6. RESULTADOS: Foram elegíveis para o estudo 39 pacientes. Destes, 32 foram investigados. Houve sensibilização ao A. fumigatus em 34%. Ambos os métodos, o critério da Cystic Fibrosis Foundation e a pesquisa de IgE específica contra antígenos recombinantes, determinaram três casos de ABPA; entretanto, o diagnóstico foi concordante em apenas dois pacientes. CONCLUSÃO: A detecção de IgE específica contra antígenos recombinantes do A. fumigatus foi ferramenta útil para detecção precoce da sensibilização e diagnóstico de ABPA. No entanto, a confirmação diagnóstica não pôde ser desvinculada da condição clínica, e sua utilização para diagnóstico, detecção de recidivas e critério de cura ainda requer estudos longitudinais, envolvendo maior número de pacientes.OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA is a complicating factor of cystic fibrosis which can result in a devastating combination as

Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

International Nuclear Information System (INIS)

Morrison, S.A.; Jesty, J.

1984-01-01

A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

Diseño y construcción de vectores de transferencia para la obtención de virus vaccinia Ankara modificado (MVA recombinantes Design and construction of transfer vectors in order to obtain recombinant modified vaccinia virus Ankara (MVA

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M. F. Ferrer

2007-09-01

Full Text Available El virus vaccinia Ankara modificado (MVA constituye un buen candidato para el desarrollo de vectores virales de expresión no replicativos porque no replica en la mayoría de las células de mamíferos. Para la producción de MVA recombinantes es fundamental disponer de vectores de transferencia que, por recombinación homóloga con el genoma viral, permitan introducir los genes de interés en regiones no esenciales para la replicación in vitro. En este trabajo se diseñaron y obtuvieron los vectores de transferencia denominados VT-MHA y VT-MTK que portan las regiones correspondientes a las posiciones 1-303 y 608-948 del gen MVA165R y 1-244 y 325-534 del gen MVA086R, respectivamente, las que flanquean un sitio de clonado múltiple para la inserción de los genes foráneos. En dichos vectores se clonaron los casetes para la expresión de los genes lac Z o uid A, y la actividad de las enzimas marcadoras b-galactosidasa y b-glucuronidasa se confirmó in situ. Además, utilizando el vector denominado VT-MTK-GUS, se obtuvieron y aislaron MVA recombinantes puros que portan y expresan el gen uid A. Los resultados obtenidos constituyen las herramientas básicas para establecer la metodología de obtención de MVA recombinantes, con el propósito de desarrollar localmente vectores virales no replicativos candidatos a vacunas.Modified Vaccinia virus Ankara (MVA constitutes a good candidate for the development of non-replicative expression viral vectors because it does not replicate in most of mammalian cells. It is essential, for the production of recombinant MVA, the availability of transfer vectors which allow the introduction of desired genes into non-essential regions for in vitro viral replication, by homologous recombination with the viral genome. In the present work, the transfer vectors named VT-MHA and VT-MTK were designed and obtained. They carried genomic regions corresponding to 1- 303 and 608-948 positions of the MVA165R gene and 1-244 and

Vanillin production by recombinant strains of Escherichia coli Produção de vanilina por linhagens recombinantes de Escherichia coli

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Attilio Converti

2003-11-01

Full Text Available Vanillin production from ferulate was studied using different recombinant strains of Escherichia coli. To prevent the occurrence of aerobic conditions and then possible product oxidation, tests were performed in Erlenmeyer flasks under mild mixing (150 rpm. Among other transformants, E. coli JM109(pBB1 appeared to be the best vanillin producer, being able to convert no less than 95% of starting ferulate to the product within 1h. This yield decreased down to 72% after 72h, likely because of a non-specific oxidase activity responsible for vanillin oxidation to vanillate.A produção de vanilina a partir de ácido ferúlico foi estudada utilizando-se diferentes linhagens recombinantes de Escherichia coli. Para prevenir a ocorrência de condições de aerobiose e a possível oxidação do produto, os ensaios foram realizados em frascos Erlenmeyer sob agitação moderada (150 rpm. E. coli JM109 (pBBI mostrou-se o melhor produtor de vanilina entre os demais agentes transformantes, sendo capaz de converter 95% do ácido ferúlico inicial em produto após 1h, rendimento este que decresceu para 72% após 72h, provavelmente devido à atividade de uma oxidase não-específica responsável pela oxidação de vanilina a ácido vanílico.

Factor VII-activating protease in patients with acute deep venous thrombosis

DEFF Research Database (Denmark)

Sidelmann, Johannes J; Vitzthum, Frank; Funding, Eva

2008-01-01

Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu......-PA, without affecting the ability to activate coagulation Factor VII (FVII). Previous studies have investigated the association of the 1601GA genotype with incidence and progression of carotid stenosis and deep venous thrombosis (DVT). The present study is the first to evaluate the potential association...... between the FSAP phenotype and DVT. We studied the association between the 1601G/A polymorphism, FSAP activity, FSAP antigen, Factor VIIa (FVIIa), prothrombin fragment 1+2 (F1+2), and C-reactive protein (CRP) in plasmas of 170 patients suspected for DVT. FSAP genotypes were equally distributed in patients...

Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report.

Science.gov (United States)

Sheth, Sujit; Soff, Gerald; Mitchell, Beau; Green, David; Kaicker, Shipra; Fireman, Fernando; Tugal, Oya; Guarini, Ludovico; Giardina, Patricia; Aledort, Louis

2012-02-01

While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient's past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

Severe perioperative bleeding in renal cell carcinoma after elective pericardiocentesis associated left ventricular puncture: case report

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Javier Lasala

2016-07-01

Full Text Available Resumen En los Estados Unidos se estimó que, durante el 2015, unos 61 560 pacientes serían diagnosticados con cáncer renal y que 14 080 morirían por esta enfermedad. Presentamos el caso de un paciente con carcinoma de células renales y trombo tumoral de vena cava inferior que sufrió una hemorragia perioperatoria grave y coagulopatía después de una esternotomía de emergencia. También abordamos aspectos relevantes del cuidado anestésico perioperatorio incluyendo consideraciones y manejo de coagulopatía, falla renal y hepática en un paciente oncológico. El caso es un hombre de 49 años que fue llevado a embolización tumoral guiada por radiología, nefrectomía radical izquierda y trombectomía de vena cava inferior. En el período postoperatorio desarrolló sepsis, falla orgánica múltiple y efusión pericárdica que requirió pericardiocentesis. Durante la pericardiocentesis sufrió perforación iatrogénica de ventrículo izquierdo que necesitó esternotomía de emergencia y reparación del ventrículo izquierdo. Los pacientes con cáncer son a menudo un reto para el equipo de cirugía y anestesia, y el cuidado de emergencia requiere un abordaje integral y organizado. El uso de factor recombinante VIIa NovoSeven puede ayudar en el manejo de la hemorragia severa perioperatoria después de cirugía cardiotorácica en pacientes oncológicos, pero se deben hacer estudios posteriores para confirmarlo.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

Science.gov (United States)

See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

2016-09-01

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

Critical appraisal of the role of recombinant activated factor VII in the treatment of hemophilia patients with inhibitors

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Ampaiwan Chuansumrit

2010-03-01

Full Text Available Ampaiwan Chuansumrit1, Pantep Angchaisuksiri2, Nongnuch Sirachainan11Departments of Pediatrics and 2Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University,  Bangkok, ThailandAbstract: Hemophilia patients with inhibitors faced the constraint of inadequate treatment for several years before the era of recombinant factor VIIa (rFVII. Initially, rFVIIa was used in the compassionate-use programs. After a worldwide license was issued, more than 1.5 million doses were administered. Bleeding of joints and muscles was controlled effectively by means of an early home treatment program, with either a standard dose of 90 μg/kg every 2 to 3 hours for a few doses or a single dose of 270 μg/kg. For more serious bleeding episodes or minor surgery, an initial dose of 90 μg/kg was given every 2 hours for 24 to 48 hours followed by increased intervals of 3 to 6 hours according to the severity of bleeding and efficacy of bleeding control. In cases of major surgery such as orthopedic procedures, the same regimen can be applied except for a higher initial dose of 120 to 180 μg/kg. However, increasing the dose should be considered if there are unexpected bleeding complications since the half-life and clearance of rFVIIa differ between individuals. In addition, prophylaxis is administered to a small number of patients. Finally, the reported thromboembolic events found in hemophilia patients with inhibitors receiving rFVIIa are extremely low, much less than 1%.Keywords: bleeding disorder, hemophilia, inhibitor, NovoSeven, recombinant factor VIIa

Pichia pastoris: una plataforma para la producción de proteínas heterólogas.

OpenAIRE

Yunier Serrano-Rivero; Karen Marrero-Domínguez; Rafael Fando-Calzada

2016-01-01

La levadura Pichia pastoris ha sido ampliamente empleada como sistema hospedero para la producción de proteínas heterólogas, tales como; fragmentos de anticuerpos, huridina recombinante, eritropoyetina humana recombinante e insulina humana recombinante. Su extendida aplicación se debe a la disponibilidad del promotor de la enzima alcohol oxidasa, el cual es fuerte y regulable por metanol y a su capacidad para alcanzar altas densidades celulares en biorreactores en medios de cultivo baratos. E...

Production of polyclonal antisera using recombinant coat proteins of Grapevine leafroll-associated virus 2 and Grapevine virus B Produção de anti-soros policlonais a partir de proteínas capsidiais recombinantes de Grapevine leafroll-associated virus 2 e Grapevine virus B

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Paula Radaelli

2008-10-01

Full Text Available The objective of this work was to produce and characterize specific antisera against Brazilian isolates of Grapevine leafroll-associated virus 2 (GLRaV-2 and Grapevine virus B (GVB, developed from expressed coat proteins (CPs in Escherichia coli, and to test their possible use for the detection of these two viruses in diseased grapevines. The coat protein (CP genes were RT-PCR-amplified, cloned and sequenced. The CP genes were subsequently subcloned, and the recombinant plasmids were used to transform E. coli cells and express the coat proteins. The recombinant coat proteins were purified, and their identities were confirmed by SDS-PAGE and Western blot and used for rabbit immunizations. Antisera raised against these proteins were able to recognize the corresponding recombinant proteins in Western blots and to detect GLRaV-2 and GVB in infected grapevine tissues, by indirect ELISA, discriminating healthy and infected grapevines with absorbances (A405 of 0.08/1.15 and 0.12/1.30, respectively. Expressing CP genes can yield high amount of viral protein with high antigenicity, and GLRaV-2 and GVB antisera obtained in this study can allow reliable virus disease diagnosis.O objetivo deste trabalho foi produzir e caracterizar anti-soros específicos contra isolados brasileiros do Vírus do enrolamento-da-folha da videira 2 (GLRaV-2 e do Vírus B da videira (GVB, desenvolvidos a partir das proteínas capsidiais expressas em Escherichia coli, e testar seu possível uso para a detecção destes dois vírus em videiras infectadas. Os genes da proteína capsidial (CP foram amplificados via RT-PCR, clonados e seqüenciados. Foram, subseqüentemente, subclonados, e os plasmídeos recombinantes foram empregados na transformação das células de E. coli e na expressão das proteínas capsidiais. As proteínas capsidiais recombinantes foram purificadas, e suas identidades foram confirmadas em SDS-PAGE e "Western blot" e utilizadas para imunizar coelhos. Os anti

Use of recombinant factor VIIA for control of combat-related haemorrhage.

Science.gov (United States)

Woodruff, Susan I; Dougherty, Amber L; Dye, Judy L; Mohrle, Charlene R; Galarneau, Michael R

2010-02-01

Recombinant activated human coagulation factor VII (rFVIIa), an intravascular strategy to promote clotting, is being used as an adjunct to surgical control of bleeding in combat trauma patients. To describe the initial experiences with rFVIIa administered to combat casualties at US Navy-Marine Corps medical treatment facilities in Iraq, and to compare survival outcomes of those treated with rFVIIa to controls not receiving rFVIIa. Medical encounter data from the US Navy-Marine Corps Combat Trauma Registry were retrospectively reviewed to identify all battle-injured patients documented as having received rFVIIa during the period May 2004 to January 2006 of Operation Iraqi Freedom. Available clinical and injury related data are presented to characterise the patients. To assess effects of rFVIIa on survival outcomes, rFVIIa cases were matched to controls on injury severity and age. 22 battle-injured patients from the Combat Trauma Registry received rFVIIa. Primarily young US Marines, these patients typically had penetrating injuries from improvised explosive devices and gunshot wounds. Injuries were often abdominal. The average dose used was similar to that reported in another study of civilian trauma patients, although dosing varies widely in the existing experimental and anecdotal literature. Over two-thirds (68%) of the rFVIIa patients survived-an identical outcome seen for a matched control group of 22 patients. Survival of seriously injured combat casualties was good, although identical to that of a control group. Methodological limitations of this retrospective study preclude making firm conclusions about the effectiveness of rFVIIa. Future controlled studies are needed for safety and efficacy testing of rFVIIa in combat trauma patients.

Optimización de una técnica de medida de disrupción endocrina por medio de Saccharomyces cerevisiae recombinantes

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Karen Keel

2011-05-01

Full Text Available Los disruptores endocrinos son sustancias químicas, exógenas al organismo, capaces de alterar la homeostasis del sistema endocrino-reproductivo. Un grupo de ellos, los compuestos estrogénicos, pueden ocasionar efectos negativos sobre la capacidad reproductiva de algunos peces, disminución de la fertilidad, la aptitud sexual y la producción de esperma y feminización de los machos. En este trabajo se describe el desempeno analítico de un método para la cuantificación de estrogenicidad en aguas. Se utilizó la técnica Yeast Estrogen Screen (YES con Saccharomyces cerevisiae recombinante, una levadura modificada genéticamente que expresa el receptor de estrógenos humano y un plasmido de expresión con el gen reportero lacZ, bajo el control de elementos de respuesta a estrógenos. Dicho gen codifica para la ƒÀ-galactosidasa, que se secreta al medio y metaboliza un sustrato cromogénico, observandose un cambio de color que se mide a 420 nm. Se utilizaron estándares de 17 ƒÀ-estradiol para realizar una curva de calibración en el rango de concentraciones entre 1.75 ng/l y 7.5 ƒÊg/l. Las curvas sigmoides dosis.respuesta obtenidas se ajustaron mediante la función de Hill y los r2 fueron mayores a 0,95. El limite de detección fue de 55 ng/l. La estrogenicidad para las muestras ensayadas fue no detectable.

RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice

Czech Academy of Sciences Publication Activity Database

Jahanban-Esfahlan, R.; Seidi, K.; Monhemi, H.; Adli, A.D.F.; Minofar, Babak; Zare, P.; Farajzadeh, D.; Farajnia, S.; Behzadi, R.; Abbasi, M.M.; Zarghami, N.; Javaheri, T.

2017-01-01

Roč. 7, AUG 15 (2017), s. 1-14, č. článku 8126. ISSN 2045-2322 Institutional support: RVO:61388971 Keywords : TISSUE-FACTOR * FACTOR-VIIA * STAPHYLOCOAGULASE Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.259, year: 2016

Evaluation of a recombinant p24 antigen for the detection of Feline Immunodeficiency Virus-specific antibodies Avaliação do antígeno recombinante p24 para a detecção de anticorpos específicos do Vírus da Imunodeficiência Felina

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Carlos Mazur

2010-10-01

Full Text Available Feline Immunodeficiency Virus is a worldwide infection and is considered a significant pathogen. The diagnosis of FIV infections is mainly based on commercially available rapid tests that are highly expensive in Brazil, hence it is rarely performed in the country. Furthermore, lentiviruses grow slowly and poorly in tissue cultures, making the production of viral antigen by classic means and thus the establishment of FIV immunodiagnosis impracticable. In order to deal with this, recombinant DNA techniques were adopted to produce the protein p24, a viral capsid antigen. The protein's reactivity evaluation analyzed by Western blot indicated that this recombinant antigen can be a useful tool for the immunodiagnostic of FIV infections.O vírus da imunodeficiência felina tem distribuição mundial e é considerado um patógeno significativo. No Brasil, a prática diagnóstica é baseada principalmente em teste rápidos, importados e de custo elevado, disponíveis comercialmente. Devido ao seu custo proibitivo em nosso país, o diagnóstico da infecção pelo FIV é raramente realizado. Ademais, os lentivírus se multiplicam lenta e pobremente em cultura de células, o que torna a produção de antígeno por meios clássicos e o estabelecimento do imunodiagnóstico impraticável. Com o objetivo de lidar com esta questão, técnicas de DNA recombinante foram utilizadas para produção de um antígeno do capsídeo viral, a proteína p24. A avaliação da reatividade realizada por Western blot indicou que este antígeno recombinante pode ser útil para o imunodiagnóstico de infecções pelo FIV.

Fermentation of sweet whey by recombinant Escherichia coli K011 Fermentação de soro de leite por Escherichia coli KO11 recombinante

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Amarildo Ricardo Leite

2000-09-01

Full Text Available The production of ethanol from sweet whey using the recombinant Escherichia coli KO11, in batch fermentation, was tested. The maximum ethanol yield was reached after 96h, representing only 38% of the theoretical yield. The supplementation of whey with components of LB broth increased the maximum yield to 96% in 72h. The addition of 0.5% yeast extract to whey resulted in maximum yield of 74% at 36h and it increased to over 100% when yeast extract and trace metals solution (Fe++, Mn++ and Zn++ were added.A produção de etanol a partir de soro de leite empregando a cepa Escherichia coli KO11 recombinante, em fermentação de batelada, foi testada. O rendimento máximo de etanol foi obtido em 96h, representando apenas 38% do rendimento teórico. A suplementação do soro com os componentes do caldo LB aumentou o rendimento para 96% em 72h. A adição de 0,5% de extrato de levedura ao soro resultou em um rendimento máximo de 74% em 36h que aumentou para acima de 100% quando se adicionou extrato de levedura e uma solução de metais traço (Fe++, Mn++ e Zn++.

EVALUACIÓN DE LA PRODUCCIÓN DE ETANOL UTILIZANDO CEPAS RECOMBINANTES DE Saccharomyces cerevisiae A PARTIR DE MELAZA DE CAÑA DE AZÚCAR

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CAROLINA PEÑA

2009-01-01

Full Text Available Se evaluó la producción de etanol, el crecimiento celular y el consumo de sustrato de tres cepas de Saccharomyces cerevisiae: CBS8066 (control y dos recombinantes desarrolladas en la Unidad de Biotecnología Vegetal de CIB, GG570-CIBI y GG570-CIBII. Dichas cepas estuvieron bajo el efecto de dos concentraciones de sacarosa (170 y 250g/L y dos sustratos (industrial con melaza caña azúcar y sintético con sacarosa. Durante la fermentación en sustrato industrial se obtuvo mayor producción de etanol a concentración de 250g sacarosa/L. Bajo estas condiciones, la cepa GG570-CIBII produjo en promedio 2,34g etanol/L mas con respecto a la cepa control y en adición, a las 10h, produjo 8,02g/L por encima de la cepa control. Por otro lado, la cepa GG570- CIBI produjo 3,46g etanol/L menos que la cepa control. De esta forma, se encontró que la cepa GG570-CIBII es tolerante a alta concentración de sacarosa, y además, es capaz de producir una concentración mayor de etanol con respecto a la cepa control en melaza caña azúcar con 250g/L sacarosa.

Teste intradérmico com proteínas recombinantes de Mycobacterium bovis como antígenos em Cavia porcellus

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Elaine S.P. Melo

2014-10-01

Full Text Available O teste intradérmico para o diagnóstico da tuberculose bovina utiliza derivados proteicos purificados (PPD de Mycobacterium bovis que são capazes de induzir reações de hipersensibilidade em animais infectados. No entanto, apresenta baixa especificidade devido à ocorrência de reações cruzadas com outras micobactérias. Neste sentido, o objetivo desse trabalho foi produzir proteínas recombinantes (ESAT-6, PE13, PE5 e ESX-1 de Mycobacterium bovis e avaliá-las como antígenos em teste intradérmico utilizando Cavia porcellus como modelo, e verificar se as condições empregadas na purificação (nativa ou desnaturante interferem no desempenho antigênico dessas proteínas. As proteínas foram testadas em Cavia porcellus previamente sensibilizados com cepa M. bovis AN5 inativada, individualmente (160 µg ou combinadas na forma de um coquetel (40 µg cada. O coquetel de proteínas induziu reações de hipersensibilidade nos animais sensibilizados significativamente superiores (p=0,002 as observadas nos animais não sensibilizados, possibilitando diferenciação. No entanto, as proteínas isoladamente não foram capazes de promover essa diferenciação. As condições de solubilização e purificação influenciaram o desempenho antigênico da proteína ESAT-6, pois, quando produzida em condição desnaturante desencadeou reações inespecíficas nos animais não sensibilizados, enquanto que aquela produzida em condições nativas e aplicada em concentrações de 6, 12, 24 e 48µg induziu reações significativas apenas nos animais sensibilizados, confirmando o seu potencial como antígeno.

Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.

Science.gov (United States)

Olson, N C; Raffield, L M; Lange, L A; Lange, E M; Longstreth, W T; Chauhan, G; Debette, S; Seshadri, S; Reiner, A P; Tracy, R P

2018-01-01

Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL -1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL -1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

Science.gov (United States)

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

International Nuclear Information System (INIS)

Thim, L.; Bjoern, S.; Christensen, M.; Nicolaisen, E.M.; Lund-Hansen, T.; Pedersen, A.H.; Hedner, U.

1988-01-01

Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VII a , participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca 2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VII a molecule, namely, 10 γ-carboxylated, N-terminally located glutamic acid residues, 1 β-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VII a as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VII a . By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradation, the protein backbone of recombinant factor VII a was found to be identical with human factor VII a . Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VII a . In the recombinant factor VII a , asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VII a and human plasma factor VII a . These results show that factor VII a as produced in the transfected baby hamster kidney cells is very similar to human plasma factor VII a and that this cell line thus might represent an alternative source for human factor VII a

Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven)

DEFF Research Database (Denmark)

Viuff, D.; Lauritzen, B.; Pusateri, A.E.

2008-01-01

BACKGROUND: A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven), may be used to improve haemostasis but potential interactions with different volume expanders...

A review of studies of the activation of the blood coagulation mechanism in chimpanzees (Pan troglodytes)

NARCIS (Netherlands)

ten Cate, H.; Schenk, B. E.; Biemond, B. J.; Levi, M. [=Marcel M.; van der Poll, T.; Buller, H. R.; ten Cate, J. W.

1994-01-01

This paper reviews our recent studies of blood coagulation activation in the chimpanzee which were carried out employing sensitive immunoassays that measure activation markers of blood coagulation in plasma. Infused factor VIIa activated both factors IX and X in vivo; this reaction depended on the

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

DEFF Research Database (Denmark)

Bosch, Jaime; Thabut, Dominique; Albillos, Agustín

2008-01-01

A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal...

Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation.

Science.gov (United States)

Mitrophanov, Alexander Y; Reifman, Jaques

2011-10-01

The therapeutic potential of a hemostatic agent can be assessed by investigating its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa)--a promising hemostasis-inducing biologic--experimental studies addressing its effects on thrombin generation yielded disparate results. To elucidate the inherent ability of rFVIIa to modulate thrombin production, it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about thrombin generation mechanisms. The existing body of knowledge about coagulation biochemistry can be rigorously represented by a computational model that incorporates the known reactions and parameter values constituting the biochemical network. We used a thoroughly validated numerical model to generate activated factor VII (FVIIa) titration curves in the cases of normal blood composition, hemophilia A and B blood, blood lacking factor VII, blood lacking tissue factor pathway inhibitor, and diluted blood. We utilized the generated curves to perform systematic fold-change analyses for five quantitative parameters characterizing thrombin accumulation. The largest fold changes induced by increasing FVIIa concentration were observed for clotting time, thrombin peak time, and maximum slope of the thrombin curve. By contrast, thrombin peak height was much less affected by FVIIa titrations, and the area under the thrombin curve stayed practically unchanged. Comparisons with experimental data demonstrated that the computationally derived patterns can be observed in vitro. rFVIIa modulates thrombin generation primarily by accelerating the process, without significantly affecting the total amount of generated thrombin. Copyright © 2011 Elsevier Ltd. All rights reserved.

Management of Labour and Delivery in a Patient With Acquired Factor VII Deficiency With Inhibitor: A Case Report.

Science.gov (United States)

Matei, Anca; Dolan, Sean; Andrews, James; Rivard, Georges-Étienne

2016-02-01

Acquired factor VII (FVII) deficiency with inhibitor increases the risk of hemorrhage during pregnancy. However, there are no published reports guiding its management in the peripartum period. A 24-year-old woman with inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no bleeding-related complications; however, the FVII level was supratherapeutic. The patient returned during a second pregnancy. A reduced dose of rFVIIa was administered. The delivery was complicated by postpartum hemorrhage, which resolved with the addition of uterotonic agents. Recombinant FVIIa and tranexamic acid offer an effective peripartum treatment in women with inhibitory antibody to FVII. Further research should delineate the optimal time of administration. Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Coagulation for the clinician

African Journals Online (AJOL)

and activates factor X at a 50 - 100-fold higher rate than the factor VIIa-tissue factor complex, ... participate in the formation of vitamin K-dependent protein complexes. .... XIII,67 which covalently cross-links the fibrin polymers both longitudinally and ...... as it deserves a new evaluation leading to a final validation. TAble I. TeG ...

Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

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Yoan Antonio Sánchez Rodríguez

2011-03-01

Full Text Available INTRODUCCIÓN: la hepatitis crónica C ha adquirido rango de pandemia. El virus de la hepatitis C se ha convertido en la causa principal de hepatitis crónica, cirrosis hepática, hepatocarcinoma, y trasplante de hígado a nivel mundial. OBJETIVO: identificar los efectos adversos asociados a la terapia combinada interferón alfa 2b recombinante más ribavirina durante la evolución del tratamiento y hasta 8 semanas después de finalizado, así como los principales efectos asociados a salidas temporales o definitivas de esta terapia. MÉTODOS: estudio de farmacovigilancia cuya serie estuvo conformada por 122 pacientes con hepatitis crónica C atendidos en el Instituto de Gastroenterología desde mayo de 2001 hasta mayo de 2006. Se utilizó interferón alfa 2b recombinante (3 millones de unidades 3 veces por semana más ribavirina (1 000 o 1 200 mg diarios en dependencia del peso corporal durante 48 semanas. RESULTADOS: el 88,5 % del total de casos presentó efectos adversos; de ellos el 79,5 % correspondió al síndrome seudogripal, seguido de manifestaciones hematológicas, neuropsiquiátricas, gastrointestinales, entre otras menos frecuentes. El 6,6 % de la serie presentó salidas temporales del tratamiento por efecto adverso distinto de la anemia y 4 pacientes, salidas definitivas del estudio, tres por anemia hemolítica severa y uno con hipertiroidismo no controlable. CONCLUSIONES: la terapia combinada interferón alfa 2b recombinante más ribavirina resulta segura, donde el mayor número de casos presentó síndrome seudogripal como efecto adverso más frecuente. Las manifestaciones hematológicas asociadas a las salidas definitivas del estudio permitieron recomendar seguimiento estricto de la hemoglobina y profundizar en el diagnóstico y tratamiento de los principales efectos adversos presentes en otros sistemas y asociados a esta terapia.INTRODUCTION: chronic hepatitis C has reached the category of pandemic. The hepatitis C virus is the

Biophysical characterisation of GlycoPEGylated recombinant human factor VIIa

DEFF Research Database (Denmark)

Plesner, Bitten; Westh, Peter; Nielsen, Anders D.

2011-01-01

The effects of GlycoPEGylation on the structural, kinetic and thermal stability of recombinant human FVIIa were investigated using rFVIIa and linear 10 kDa and branched 40 kDa GlycoPEGylated® recombinant human FVIIa derivatives. The secondary and tertiary structure of rFVIIa measured by circular...... dichroism (CD) was maintained upon PEGylation. In contrast, the thermal and kinetic stability of rFVIIa was affected by GlycoPEGylation, as the apparent unfolding temperature Tm measured by differential scanning calorimetry (DSC) and the temperature of aggregation, Tagg, measured by light scattering (LS......) both increased with GlycoPEGylation. Both Tm and Tagg were independent of the molecular weight and the shape of the PEG chain. From the present biophysical characterisation it is concluded that after GlycoPEGylation, rFVIIa appears to be unaffected structurally (secondary and tertiary structure...

Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

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Manash S Chatterjee

2010-09-01

Full Text Available Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF, human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa will generate thrombin after an initiation time (T(i of 1 to 2 hours (depending on donor, while activation of platelets with the GPVI-activator convulxin reduces T(i to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen, and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai. This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds

Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

Energy Technology Data Exchange (ETDEWEB)

Tormoen, Garth W.; Cianchetti, Flor A. [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Bock, Paul E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); McCarty, Owen J. T., E-mail: tormoeng@ohsu.edu [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR (United States); Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR (United States)

2012-09-06

Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

ANALYSIS OF Treponema pallidum RECOMBINANT ANTIGENS FOR DIAGNOSIS OF SYPHILIS BY WESTERN BLOTTING TECHNIQUE Análise de antígenos recombinantes de Treponema pallidum no diagnóstico da sífilis utilizando a técnica de Western Blotting

Directory of Open Access Journals (Sweden)

Neuza Satomi SATO

1999-03-01

Full Text Available Three GST fusion recombinant antigen of Treponema pallidum, described as GST-rTp47, GST-rTp17 and GST-rTp15 were analyzed by Western blotting techniques. We have tested 53 serum samples: 25 from patients at different clinical stages of syphilis, all of them presenting anti-treponemal antibody, 25 from healthy blood donors and three from patients with sexually transmitted disease (STD other than syphilis. Almost all samples from patients with syphilis presented a strong reactivity with GST-rTp17 antigen. Some samples were non-reactive or showed a weak reaction with GST-rTp47 and/or GST-rTp15, and apparently there was no correlation with the stage of disease. There was no seropositivity among blood donors. No sample reacted with purified GST. We concluded that due to their specificity these recombinant antigens can be used as GST fusion protein for development of syphilis diagnostic assays.Os antígenos recombinantes de Treponema pallidum GST-rTp47, GST-rTp17 e GST-rTp15, produzidos em fusão com glutationa S-transferase (GST em E. coli, foram analisados quanto ao potencial diagnóstico da sífilis pela técnica de Western blotting. Foram testadas 53 amostras, sendo 25 de pacientes em diferentes estágios clínicos da sífilis, com resultados positivos no teste treponêmico clássico; 25 amostras procedentes de doadores de banco de sangue, com sorologia negativa e 3 de pacientes com doença sexualmente transmissível não relacionado à sífilis. Todas as amostras de pacientes com sífilis apresentaram alta reatividade com o antígeno GST-rTp17. Quanto aos antígenos GST-rTp47 e GST-Tp15 verificou-se uma variação na presença ou na intensidade da reação em diferentes amostras de pacientes com sífilis, sem mostrar correlação com o estágio da doença. Nenhuma reatividade contra quaisquer desses antígenos foi observada com as amostras do grupo controle. Nenhuma das amostras testadas apresentaram reatividade com a GST purificada. A

Validación de un ELISA para la cuantificación de las impurezas proteicas de la cepa hospedera en el principio activo de la vacuna recombinante cubana contra la hepatitis B

Directory of Open Access Journals (Sweden)

Eliana Pérez

2014-04-01

Full Text Available Se validó un inmunoensayo tipo sandwich de doble anticuerpo para cuantificar las impurezas proteicas de la cepa hospedera que pueden estar presentes en el principio activo de la vacuna cubana contra la hepatitis B. Se prepararon los reactivos biológicos empleados en el ELISA. Las proteínas de la cepa hospedera se obtuvieron bajo las mismas condiciones que el proceso de producción de la proteína recombinante hasta un paso de semipurificación o purificación primaria. Los antisueros dirigidos contra las proteínas de la cepa hospedera se generaron en conejos por un proceso de inmunización en cascada. Para la validación se analizaron los siguientes parámetros: linealidad, límite de detección y cuantificación, exactitud, rango y precisión. El ensayo establecido resultó específico, con una exactitud entre 89% y 109% para todos los tampones estudiados; se demostró un ajuste parabólico y un rango de trabajo entre 0,63 y 1,25 ng/mL, la repetibilidad y la precisión intermedia mostraron coeficientes de variación inferiores al 10 y 20% respectivamente.

Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue factor pathway inhibitor under static and shear conditions in vitro.

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Sara P Y Che

Full Text Available Mammary tumors and malignant breast cancer cell lines over-express the coagulation factor, tissue factor (TF. High expression of TF is associated with a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI, the endogenous inhibitor of TF, is constitutively expressed on the endothelium. We hypothesized that TF-expressing tumor cells can bind to immobilized recombinant TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the adhesion of breast cancer cells to immobilized TFPI under static and shear conditions (0.35 - 1.3 dyn/cm2. We found that high-TF-expressing breast cancer cells, MDA-MB-231 (with a TF density of 460,000/cell, but not low TF-expressing MCF-7 (with a TF density of 1,400/cell, adhered to recombinant TFPI, under static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required activated factor VII (FVIIa, but not FX, and was inhibited by a factor VIIa-blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the TFPI-coating concentration, FVIIa concentration and shear stress, with no observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first study showing that TF-expressing tumor cells can be captured by immobilized TFPI, a ligand constitutively expressed on the endothelium, under low shear in vitro. Based on our results, we hypothesize that TFPI could be a novel ligand mediating the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under conditions of low shear during metastasis.

[Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery].

Science.gov (United States)

Carneiro, João Miguel Gonçalves Valadares de Morais; Alves, Joana; Conde, Patrícia; Xambre, Fátima; Almeida, Emanuel; Marques, Céline; Luís, Mariana; Godinho, Ana Maria Mano Garção; Fernandez-Llimos, Fernando

Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM ® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10g.dL -1 and the other blood products by routine coagulation and ROTEM ® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

Science.gov (United States)

Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

2017-11-01

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

Producción de anticuerpos policlonales IgG contra una proteína con actividad de óxido nítrico sintetasa de Toxoplasma gondii recombinante (NOS-Tg-r y marcación inmunológica en taquizoítoso Production of Polyclonal Antibodies against Toxoplasma gondii Recombinant protein with Nitric Oxide Synthase activity and immunologic marking in Tachyzoites

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Jonathan Mauricio Padilla-Londoño

2008-06-01

Full Text Available La enzima óxido nítrico sintetasa ha sido estudiada en mamíferos; en los últimos años se ha descrito que existe también en protozoos, pero se desconocen aspectos importantes de su función. Se logró producir anticuerpos policlonales contra la proteína recombinante con actividad de óxido nítrico sintetasa (NOS-Tg-r de Toxoplasma gondii y realizar marcación inmunológica en taquizoítos. Se usaron dos conejos Nueva Zelanda (Oryctolagus cuniculusque se inmunizaron por vía intramuscular con NOS-Tg-r, y dos tipos de adyuvantes, hidróxido de aluminio y adyuvante de Freund. Se comprobó la presencia de anticuerpos policlonales con la técnica de ensayo inmunoenzimático indirecto. Los resultados obtenidos mostraron que a NOS-Tg-r con adyuvante de Freund indujo mayor respuesta inmune que la de la NOS-Tg-r con hidróxido aluminio p 0,005. Para verificar si había reacción cruzada, se realizó una prueba ELISA utilizando como antígenos: metaloproteasa de T. gondii recombinante, cisteína proteasa 5 de Entamoeba histolytica recombinante, albúmina al 2%, hidróxido de aluminio y adyuvante de Freund. Los valores obtenidos con sueros preinmunes y contra proteínas alternas no superaron el punto de corte (0,069, lo cual indica que los anticuerpos policlonales obtenidos son específicos para NOS-Tg-r. Se realizó marcación inmunológica en taquizoítos de Toxoplasma gondii con inmunofluorescencia indirecta que mostró una marcación difusa a nivel de citoplasma y confirmó la presencia de esta proteína en los taquizoítos.The nitric oxide synthase (NOSis an enzyme well described on mammals but little is known about the role of these enzymes on pathogenic parasites. We produced polyclonal antibodies against a recombinant NOS enzyme from Toxoplasma gondii nd e lso er formed n mmunol locali zation of the enzyme on tachyzoites. We used two New Zealand rabbits (Oryctolagus cuniculus to perform intramuscular immunization and we used two types of

Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

Science.gov (United States)

Mousavi Hosseini, Kamran; Nasiri, Saleh

2015-01-01

Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

Efecto de adición de iones hierro y zinc sobre la producción de etanol de dos cepas recombinantes de Saccharomyces cerevisiae

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Carolina Peña Serna

2010-01-01

Full Text Available La producción de etanol por fermentación es influenciada por la presencia de iones metálicos como hierro y zinc dado que son cofactores de la enzima alcohol deshidrogenasa. El estudio de este efecto permitiría identificar el comportamiento de los microorganismos fermentadores en sustratos industriales que contienen altas concentraciones de este tipo de iones. Este trabajo evaluó la producción de biomasa, los azúcares residuales y la producción de etanol por fermentación de tres cepas de S. cerevisiae, CBS8066, recombinantes GG570-CIBI y GG570-CIBII, bajo el efecto de la adición de hierro a 0, 50 y 150 M, y zinc a 0 y 50 M. Las cepas presentaron inhibición en la producción de biomasa y etanol bajo efecto de iones de hierro y zinc, siendo dicha inhibición mayor al estar en presencia de zinc o alta concentración de hierro. GG570-CIBI mostró disminución en producción de biomasa de 4 g/L y una caída en producción de etanol de 40% en el tratamiento 150 M hierro-50 M zinc (con respecto al tratamiento basal. GG570-CIBII fue la menos afectada con inhibición en la producción de etanol inferior a 11% a las 20 h de fermentación. Adicionalmente, presentó la mayor producción de etanol cuando hubo adición de 150 M Fe con o sin adición de zinc, siendo dicha producción entre un 9 y 14% superior a la de las cepas CBS8066 y GG570-CIBI respectivamente, bajo las mismas condiciones. Posteriormente, GG570-CIBII será evaluada en sustratos industriales debido a su menor inhibición en la producción de etanol, permitiendo así obtener mejores rendimientos.

Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF.

Science.gov (United States)

Yatuv, Rivka; Robinson, Micah; Dayan, Inbal; Baru, Moshe

2010-02-01

Improving the pharmacodynamics of protein drugs has the potential to improve the care and the quality of life of patients suffering from a variety of diseases. Four approaches to improve protein drugs are described: PEGylation, amino acid substitution, fusion to carrier proteins and encapsulation. A new platform technology based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip) is then presented. Binding of proteins to PEGLip is non-covalent, highly specific and dependent on an amino acid consensus sequence within the proteins. Association of proteins with PEGLip results in substantial enhancement of the pharmacodynamic properties of proteins following administration. This has been demonstrated in preclinical studies and clinical trials with coagulation factors VIII and VIIa. It has also been demonstrated in preclinical studies with granulocyte colony-stimulating factor. A mechanism is presented that explains the improvements in hemostatic efficacy of PEGLip-formulated coagulation factors VIII and VIIa. The reader will gain an understanding of the advantages and disadvantages of each of the approaches discussed. PEGLip formulation is an important new approach to improve the pharmacodynamics of protein drugs. This approach may be applied to further therapeutic proteins in the future.

Hemofilia A adquirida Acquired hemophilia A

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Delfina Almagro Vázquez

2010-12-01

Full Text Available La hemofilia A adquirida (HAA es un trastorno hemorrágico poco frecuente caracterizado por la presencia de autoanticuerpos contra el factor VIII (FVIII circulante. Aproximadamente en la mitad de los casos se ha observado un grupo heterogéneo de procesos patológicos que incluyen, entre otros, enfermedades autoinmunes y malignas y durante el embarazo, parto y puerperio. Las manifestaciones hemorrágicas son variables y fundamentalmente de tipo cutáneo mucoso. El diagnóstico se basa en el hallazgo en un paciente con manifestaciones hemorrágicas, prolongación del tiempo parcial de tromboplastina activado (TPTA, disminución de la actividad del FVIII y presencia de inhibidores del FVIII. El tratamiento de HAA incluye el control de las manifestaciones hemorrágicas y la supresión de la producción del anticuerpo. El concentrado de factor VIIa recombinante (FVIIar y el concentrado de complejo protrombínico (CCPA se consideran el tratamiento antihemorrágico de primera línea. Como terapéutica alternativa, en algunos casos puede utilizarse el concentrado de FVIII, la plasmaféresis y la inmunoadsorción extracorpórea. La prednisona sola o asociada con la ciclofosfamida, constituye el tratamiento inmunosupresor de primera línea. En pacientes refractarios puede administrarse como terapéutica de segunda línea, el rituximab (anti-CD20. Con la azatiopina, la ciclosporina, la vincristina y el micofenolato de mofetil, se han obtenido resultados variables.Acquired hemophilia A (AHA is an uncommon hemorrhagic disorder characterized by presence of autoantibodies to circulating factor VIII. Approximately in half of cases it is noted a heterogeneous group of pathological processes including among others, autoimmune and malignant diseases and during pregnancy, labor and puerperium. Hemorrhagic manifestations are variable and mainly of mucous cutaneous type. Diagnosis is based on the finding of a patient presenting with hemorrhagic manifestations

Producción de la proteína de choque térmico HSC70 Recombinante en Escherichia Coli BL21 (DE3 para generar anticuerpos policlonales

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Rocio Cely Castro

2006-07-01

Full Text Available Antecedentes. Los organismos vivos responden al estrés aumentando la síntesis de proteínas. El estrés por choque térmico ha sido el más estudiado y las proteínas que se inducen, se han denominado genéricamente como proteínas de choque térmico. Objetivo.En este trabajo se establecieron las condiciones óptimas de producción de la proteína HSC70, expresada en E.coli BL21 (DE3 y de los anticuerpos policlonales que permitan identificarla. Material y métodos. Mediante varios ensayos se establecieron las concentraciones óptimas del agente inductor isopropil- -D-thiogalacto­piranosido (PTG, del inóculo bacteriano, de empleo de los plásmidos de expresión pET-3a y pET-28a (+; y el método más eficiente para la recuperación de las formas soluble o insoluble de la proteína y de anticuerpos policlonales que la identifiquen. Resultados. Encontramos que el inóculo de cinco colonias con IPTG (2mM en tubos con cinco mililitros de medio modificado e incubadas por 24 horas a 37°C con agitación constante (200 r.p.m y tratamiento de sonicación, produce el mejor rendimiento de HSC70. La calidad de la proteína inducida se estableció mediante "Western blotting". Conclusión. La proteína recombinante así obtenida permitió, generar anticuerpos policlonales que a su vez permiten detectar la proteína HSC70 natural en la membrana citoplasmática de diferentes células por inmunofluorescencia, en ELISA, en Western Blot y en pruebas de bloqueo de infección de rotavirus.

Management of Surgical Third Lower Molar Extraction and Postoperative Progress in Patients With Factor VII Deficiency: A Clinical Protocol and Focus on This Rare Pathologic Entity.

Science.gov (United States)

Passarelli, Pier Carmine; Pasquantonio, Guido; D'Addona, Antonio

2017-10-01

The purpose of the present study was to analyze the management of surgical third molar extraction and postoperative progress in patients with a diagnosis of factor VII deficiency. Close collaboration between the oral-maxillofacial surgeon and hematologist will allow the team to categorize the risk and operate safely, thereby minimizing the incidence and severity of intraoperative and postoperative complications. The present retrospective study included 7 patients with factor VII deficiency who had undergone third lower molar surgery. Their factor VII deficiency ranged from 10.5 to 21.0%. Recombinant activated factor VII (rFVIIa) (coagulation factor VIIa [recombinant]; NovoSeven RT; Novo Nordisk, Bagsvaerd, Denmark) was transfused intravenously in a single dose of 25 μg/kg body weight, 30 minutes before surgical extractions. After the surgery, betamethasone, an analgesic, and an ice pack were administered. Pretreatment with recombinant activated factor VII resulted in excellent hemostasis. No hemorrhagic complications and no postoperative major bleeding were observed. The extraction of the third lower molar appears to be a safe procedure for patients with factor VII deficiency when appropriate prophylaxis with rFVIIa is used. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Synthesis, purification, and characterization of an Arg152 → Glu site-directed mutant of recombinant human blood clotting factor VII

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Berkner, K.L.

1990-01-01

Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg 152 -Ile 153 . Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg 152 → Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M r ∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

Field evaluation of safety during gestation and horizontal spread of a recombinant differential bovine herpesvirus 1 (BoHV-1 vaccine Avaliação a campo da segurança para vacas prenhes e capacidade de disseminação horizontal de uma vacina diferencial recombinante contra o Herpes-vírus Bovino tipo 1 (BoHV-1

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Fernando R. Spilki

2005-03-01

indicate that, under the conditions of the present study, the gE- vaccine virus did not cause any noticeable harmful effect on pregnant dams and on its offspring and did not spread horizontally among cattle.Infecções pelo herpesvírus bovino tipo 1 (BoHV-1 são importantes causas de doença respiratória, reprodutiva e abortos em bovinos. A vacinação é freqüentemente empregada para minimizar as perdas produzidas pela infecção. Todavia, a imunização de vacas durante a prenhez com algumas vacinas contendo vírus vivo modificado (MLV pode ocasionalmente causar abortos. Em trabalho prévio, nosso grupo desenvolveu uma vacina recombinante de BoHV-1 construída a partir de um isolado brasileiro de BoHV-1 (Franco et al., 2002a do qual o gene que codifica para a glicoproteína E (gE foi artificialmente deletado. Tal recombinante (gE- vem sendo avaliado como vacina diferencial, isto é, capaz de permitir a diferenciação entre animais vacinados e infectados. No presente estudo, o potencial de disseminação do vírus recombinante foi avaliado em um rebanho de gado de corte, em condições de campo. Para tanto, a segurança da vacina gE- quando aplicada durante a prenhez foi avaliada pela inoculação intramuscular de 10(7,4 doses infectantes para 50% dos cultivos celulares (DICC50 do vírus em 22 fêmeas prenhes (14 previamente soronegativas e 8 previamente soropositivas para BoHV-1 em diferentes fases da gestação. Outras 15 vacas prenhes foram mantidas como controles não-vacinados. Não ocorreram abortos, natimortos ou anormalidades fetais em nenhum dos grupos. Soroconversão foi observada nas fêmeas vacinadas previamente soronegativas. Em um segundo experimento, 4 novilhas foram inoculadas pela via intranasal com 10(7,6 DICC50 do vírus recombinante, sendo mantidos em contato com 16 novilhas em uma área de campo, a uma densidade de 1 animal por hectare. Os animais foram monitorados quanto à presença de sinais clínicos; amostras de soro foram coletadas nos dias

Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

DEFF Research Database (Denmark)

Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

2013-01-01

Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

Synthesis, purification, and characterization of an Arg sub 152 yields Glu site-directed mutant of recombinant human blood clotting factor VII

Energy Technology Data Exchange (ETDEWEB)

Wildgoose, P.; Kisiel, W. (Univ. of New Mexico, Albuquerque (USA)); Berkner, K.L. (ZymoGenetics, Inc., Seattle, WA (USA))

1990-04-03

Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg{sub 152}-Ile{sub 153}. Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg{sub 152} {yields} Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M{sup r}{approx}40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX.

More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate.

Science.gov (United States)

Lindahl, Tomas L; Wallstedt, Maria; Gustafsson, Kerstin M; Persson, Egon; Hillarp, Andreas

2015-03-01

The number of patients on antithrombotic treatment due to atrial fibrillation and venous thromboembolism is increasing fast due to an aging population. A growing proportion will be treated with novel oral anticoagulants, the first in clinical use was the direct oral thrombin inhibitor dabigatran (Pradaxa®). A small percentage of the patients on dabigatran will experience serious bleeding or be in need of urgent surgery. The aim of this study was to test the effects of different hemostatic agents in potentially reversing the anticoagulant effects in vitro in blood or platelet-rich plasma (PRP) spiked with dabigatran. Whole blood or PRP was spiked with the active substance dabigatran, 200 μg/L. We measured clotting time being induced by 1.4 pmol/L tissue factor using the instrument ReoRox2™ and initial clot growth velocity from a tissue factor covered surface using the instrument Thrombodynamics Analyzer T-2™. Dabigatran prolonged clotting time 5-fold but reduced clot growth velocity only slightly. The reversing effects of prothrombin complex concentrates (PCC), activated PCC (APCC) and recombinant activated factor VII (rFVIIa) were then tested. APCC (1.8 U/mL) reduced the prolonged clotting time by 1/3, rFVIIa (2 μg/L) only slightly (n = 10-20). The reduction was not significant using Mann-Whitney test but significant using t-test with Bonferronis' correction for multiple comparisons, whereas PCC (0.56 U/mL) had no effect on clotting time. APCC doubled initial clot growth velocity, although even more in the absence of dabigatran. In conclusion, APCC and rFVIIa, but not PCC, seem to reverse, at least partially, some effects of dabigatran on coagulation parameters. Systematic evaluation of case reports, registries and, ultimately, randomized clinical trials are needed to elucidate potential benefit for patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

Science.gov (United States)

Limentani, S A; Gowell, K P; Deitcher, S R

1995-04-01

This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor VIIa could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: A randomized controlled trial

NARCIS (Netherlands)

Mennen, L.; Maat, M. de; Meijer, G.; Zock, P.; Grobbee, D.; Kok, F.; Kluft, C.; Schouten, E.

1998-01-01

A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and

Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation

International Nuclear Information System (INIS)

O'Hara, P.J.; Grant, F.J.; Haldeman, B.A.; Gray, C.L.; Insley, M.Y.; Hagen, F.S.; Murray, M.J.

1987-01-01

Activated factor VII (factor VIIa) is a vitamin K-dependent plasma serine protease that participates in a cascade of reactions leading to the coagulation of blood. Two overlapping genomic clones containing sequences encoding human factor VII were isolated and characterized. The complete sequence of the gene was determined and found to span about 12.8 kilobases. The mRNA for factor VII as demonstrated by cDNA cloning is polyadenylylated at multiple sites but contains only one AAUAAA poly(A) signal sequence. The mRNA can undergo alternative splicing, forming one transcript containing eight segments as exons and another with an additional exon that encodes a larger prepro leader sequence. The latter transcript has no known counterpart in the other vitamin K-dependent proteins. The positions of the introns with respect to the amino acid sequence encoded by the eight essential exons of factor VII are the same as those present in factor IX, factor X, protein C, and the first three exons of prothrombin. These exons code for domains generally conserved among members of this gene family. The comparable introns in these genes, however, are dissimilar with respect to size and sequence, with the exception of intron C in factor VII and protein C. The gene for factor VII also contains five regions made up of tandem repeats of oligonucleotide monomer elements. More than a quarter of the intron sequences and more than a third of the 3' untranslated portion of the mRNA transcript consist of these minisatellite tandem repeats

Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation

Science.gov (United States)

Iglói, Kinga; Doeller, Christian F.; Paradis, Anne-Lise; Benchenane, Karim; Berthoz, Alain; Burgess, Neil; Rondi-Reig, Laure

2015-01-01

To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: place-based navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task. PMID:24947462

Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery

DEFF Research Database (Denmark)

Hvas, Anne-Mette; Andreasen, Jo B; Christiansen, Kirsten

2013-01-01

cardiac surgery. The haemostatic potential of various factor concentrates (fibrinogen concentrate, recombinant factor VIIa and factor XIII), fresh frozen plasma (FFP), pooled platelets and tranexamic acid was investigated. After surgery, the coagulation profiles revealed significantly prolonged clotting...... of fibrinogen concentrate, FFP or tranexamic acid improved clot stability significantly. Whole blood coagulation was significantly impaired after cardiac surgery in children. Ex-vivo studies showed a total reversal of the coagulopathy after addition of pooled platelets and significantly improved clot stability...... after addition of fibrinogen concentrate, FFP and tranexamic acid, respectively....

The molar hydrodynamic volume changes of factor VIIa due to GlycoPEGylation

DEFF Research Database (Denmark)

Plesner, Bitten; Westh, Peter; Hvidt, Søren

2011-01-01

The effects of GlycoPEGylation on the molar hydrodynamic volume of recombinant human rFVIIa were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10 kDa PEG and a branched 40 kDa PEG, respectively. Molar hydrodynamic volumes were determined by capillary......, that the molar hydrodynamic volume of the conjugated protein is not just an addition of the molar hydrodynamic volume of the PEG and the protein. The molar hydrodynamic volume of the GlycoPEGylated protein is larger than the volume of its composites. These results suggest that both the linear and the branched...

The molar hydrodynamic volume changes of factor VIIa due to GlycoPEGylation.

Science.gov (United States)

Plesner, Bitten; Westh, Peter; Hvidt, Søren; Nielsen, Anders D

2011-06-01

The effects of GlycoPEGylation on the molar hydrodynamic volume of recombinant human rFVIIa were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10kDa PEG and a branched 40kDa PEG, respectively. Molar hydrodynamic volumes were determined by capillary viscometry and mass spectrometry. The intrinsic viscosities of rFVIIa, its two GlycoPEGylated compounds, and of linear 8kDa, 10kDa, 20kDa and branched 40kDa PEG polymers were determined. The measured intrinsic viscosity of rFVIIa is 6.0mL/g, while the intrinsic viscosities of 10kDa PEG-rFVIIa and 40kDa PEG-rFVIIa are 29.5mL/g and 79.0mL/g, respectively. The intrinsic viscosities of the linear PEG polymers are 20, 22.6 and 41.4mL/g for 8, 10, and 20kDa, respectively, and 61.1mL/g for the branched 40kDa PEG. From the results of the intrinsic viscosity and MALDI-TOF measurements it is evident, that the molar hydrodynamic volume of the conjugated protein is not just an addition of the molar hydrodynamic volume of the PEG and the protein. The molar hydrodynamic volume of the GlycoPEGylated protein is larger than the volume of its composites. These results suggest that both the linear and the branched PEG are not wrapped around the surface of rFVIIa but are chains that are significantly stretched out when attached to the protein. Copyright © 2011 Elsevier B.V. All rights reserved.

Desarrollo de vacunas contra el virus de la inmunodeficiencia humana tipo 1: Relevancia de la inmunidad celular contra subtipos

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Ana María Rodríguez

2010-12-01

Full Text Available Han pasado casi 30 años de la detección de los primeros casos de infección con HIV-1 y aún no se ha conseguido desarrollar una vacuna efectiva y segura. A pesar del impacto positivo sobre la pandemia que se ha conseguido gracias a los avances en la terapia antirretroviral (TARV, el HIV/sida sigue constituyendo un grave problema para la salud pública, especialmente en los países en desarrollo, donde es difícil el acceso al tratamiento. En el mundo, 33 millones de personas viven con el virus del sida, mientras que en la Argentina se calcula que habría unos 120 000 infectados. Uno de los desafíos para lograr una vacuna contra el HIV es la variabilidad viral. El grupo M, responsable de la pandemia, se encuentra dividido en 10 subtipos y varios sub-subtipos, además de las 48 formas recombinantes circulantes y más de cien formas recombinantes únicas. La epidemia de HIV en nuestro país es tan compleja como en el resto del mundo, con la co-circulación principalmente de virus pertenecientes al subtipo B y recombinantes BF (CRF12_BF y derivadas. A pesar de la cantidad de trabajos dedicados a la caracterización de la respuesta inmune y al desarrollo de vacunas, no queda claro cuál es el impacto de la variabilidad en la elección del antígeno. Trabajos realizados en nuestro laboratorio demuestran el papel que juega la inmunidad celular con respecto a las variantes recombinantes BF, tanto en humanos como en modelos animales. Estos resultados son de importancia en el desarrollo de futuras vacunas para nuestra región.

Efecto de la recombinación de segmentos genómicos de betanodavirus en la adaptación del virus a su huésped

OpenAIRE

Souto Pereira, Sandra

2015-01-01

En este trabajo se estudian los factores implicados en la patogénesis de cepas recombinantes de betanodavirus en lenguado y rodaballo. Los betanodavirus (familia Nodaviridae) son los virus causantes de la necrosis nerviosa viral (VNN), una de las enfermedades virales más serias que afecta a larvas y juveniles de numerosas especies de peces marinos en todo el mundo. Su genoma está formado por dos moléculas de ARN monocatenal ARN1 y ARN2 que codifican la polimerasa viral y la proteína de la cáp...

Factor VII Tokushima: the first case of factor VII Cys22Gly with the development of myocardial infarction in the proband receiving recombinant factor VIIa replacement therapy.

Science.gov (United States)

Shigekiyo, Toshio; Sekimoto, Etsuko; Shibata, Hironobu; Ozaki, Shuji; Okumura, Takanobu; Fujinaga, Hiroyuki; Shibata, Hiroshi; Aihara, Ken-ichi; Akaike, Masashi

2015-12-01

An 81-year-old man was referred to our department because of suspected factor VII (FVII) deficiency. His FVII activity was under 1%, whereas the FVII activity levels of his son and granddaughter were 65 and 109%, respectively. The nucleotide at position 3886 of his FVII gene was homozygous for G. A single T to G substitution results in the replacement of wild-type Cys at residue 22 by Gly. His son was heterozygous for G and T at position 3886, whereas his granddaughter was homozygous for wild-type T. These results suggest that he was homozygous for FVII Cys22Gly. He underwent radiofrequency ablation (RFA) for hepatocellular carcinoma, receiving 20 μg/kg of recombinant FVIIa prior to RFA and 10 μg/kg of recombinant FVIIa twice after RFA. He showed no bleeding tendency; however, a myocardial infarction was diagnosed and percutaneous coronary intervention was performed.

The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells.

Science.gov (United States)

Zou, Junhuang; Chen, Qian; Almishaal, Ali; Mathur, Pranav Dinesh; Zheng, Tihua; Tian, Cong; Zheng, Qing Y; Yang, Jun

2017-02-01

Usher syndrome (USH) is the most common cause of inherited deaf-blindness, manifested as USH1, USH2 and USH3 clinical types. The protein products of USH2 causative and modifier genes, USH2A, ADGRV1, WHRN and PDZD7, interact to assemble a multiprotein complex at the ankle link region of the mechanosensitive stereociliary bundle in hair cells. Defects in this complex cause stereociliary bundle disorganization and hearing loss. The four USH2 proteins also interact in vitro with USH1 proteins including myosin VIIa, USH1G (SANS), CIB2 and harmonin. However, it is unclear whether the interactions between USH1 and USH2 proteins occur in vivo and whether USH1 proteins play a role in USH2 complex assembly in hair cells. In this study, we identified a novel interaction between myosin VIIa and PDZD7 by FLAG pull-down assay. We further investigated the role of the above-mentioned four USH1 proteins in the cochlear USH2 complex assembly using USH1 mutant mice. We showed that only myosin VIIa is indispensable for USH2 complex assembly at ankle links, indicating the potential transport and/or anchoring role of myosin VIIa for USH2 proteins in hair cells. However, myosin VIIa is not required for USH2 complex assembly in photoreceptors. We further showed that, while PDZ protein harmonin is not involved, its paralogous USH2 proteins, PDZD7 and whirlin, function synergistically in USH2 complex assembly in cochlear hair cells. In summary, our studies provide novel insight into the functional relationship between USH1 and USH2 proteins in the cochlea and the retina as well as the disease mechanisms underlying USH1 and USH2. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of indirect ELISA based on recombinant protein NcSRS2 and IFAT for detection of Neospora caninum antibodies in sheep Comparação entre ELISA baseado no antígeno recombinante NcSRS2 e RIFI para detecção de anticorpos de Neospora caninum em ovinos

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Renato Andreotti

2009-06-01

Full Text Available Neospora caninum, an Apicomplexan parasite that can causes abortion, is responsible for considerable economic and reproductive losses in livestock. The purpose of the present study was to determine whether recombinant NcSRS2 is a suitable indirect ELISA antigen for determining specific immune response to N. caninum in sheep. A total of 441 serum samples were subjected to IFAT and rNcSRS2 based-ELISA, with both tests performing similarly. The sensitivity and specificity of indirect ELISA were 98.6 and 98.3%, respectively. The kappa index shows 0.98 concordance between the two tests, which is considered excellent. Seroprevalences of 30.8 and 32.0% were detected by IFAT and indirect ELISA, respectively, showing these tests did not differ significantly on this measure (p > 0.05. Serological analysis showed that HisG tag was detected by Western Blotting recognizing rNcSRS2 protein. The potential value of rNcSRS2-based ELISA as a highly specific and sensitive tool for serological diagnosis is also supported by the strong agreement found between IFAT and ELISA. The results support the potential use of recombinant protein NcSRS2 as an antigen in indirect ELISA in sheep.Neospora caninum é um parasito Apicomplexa que pode causar abortos e é reconhecido como agente importante responsável por perdas econômicas e reprodutivas. Este estudo avaliou a proteína recombinante NcSRS2 como antígeno para ELISA indireto na determinação de resposta imune para N. caninum em ovinos. 441 amostras de soro foram analisadas por IFAT e ELISA indireto com rNcSRS2 e ambos os testes revelaram comportamento similar. A sensibilidade e especificidade de ELISA indireto foram 98,6 e 98,3%, respectivamente. O índice kappa mostrou uma concordância entre os dois testes com valor de 0,98, que é considerado excelente. Prevalências de 30,8 e 32,0% detectadas por IFAT e ELISA indireto, respectivamente, mostraram que os testes não diferiram significativamente nesse aspecto (P

Caracterización estructural del factor estimulador de colonias de los granulocitos, Hebervital

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Natacha Pérez

2014-04-01

Full Text Available El factor estimulador de colonias de granulocitos (G-CSF es un medicamento que pertenece a un grupo de proteínas hematopoyéticas. Se obtiene por vía recombinante en el Centro de Ingeniería Genética y Biotecnología, de Cuba, desde el año 2000 y es comercializado como Hebervital. Se indica a pacientes con neoplasias afectados de neutropenia febril, con tratamiento mielosupresor, seguido de trasplante de la médula ósea, entre otros. Induce alteraciones en la actividad biológica de los neutrófilos maduros que pudieran aumentar la defensa del huésped en respuesta a patógenos, como bacterias y hongos. En este trabajo se realizó un análisis específico del G-CSF para determinar su pureza y caracterización; además, se demostró su posible comparabilidad con productos de otras firmas comerciales. El patrón de bandas de las muestras en la electroforesis, así como el porcentaje del área y los perfiles cromatográficos bajo la curva en la cromatografía líquida de alta resolución, fueron similares entre los diferentes productos. La digestión enzimática y la separación proteolítica de los péptidos generaron mapas peptídicos reproducibles y de elevada similitud con el Neupogen.

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

Science.gov (United States)

Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

2016-01-01

Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Producción y caracterización de un anticuerpo policlonal dirigido contra la fosfoproteína del virus de la rabia

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Nadia Yadira Castañeda

2007-06-01

Materiales y métodos. El gen P que codifica para la proteína P del virus de la rabia, fue amplificado por reacción en cadena de la polimerasa de transcriptasa reversa y clonado en el vector de expresión PinPointTM Xa-1 T (PROMEGA. La proteína recombinante P fue expresada en E. coli purificada por cromatografía de afinidad y usada para la producción del anticuerpo policlonal anti-P. El anticuerpo obtenido fue purificado y caracterizado por inmunocitoquímica con un sistema enzimático, inmunofluorescencia, Cell-ELISA fluorométrica y Western blotting. Resultados. La proteína recombinante se expresó eficientemente como una proteína de fusión biotinilada de aproximadamente 50 kd, que corresponde a la forma completa de la proteína P del virus de la rabia. El anticuerpo policlonal anti-P detectó con alta especificidad la proteína P en cultivos de neuronas sensoriales infectados con el virus de la rabia. Conclusión. La proteína P recombinante expresada en E. coli se constituyó en un antígeno específico para producir un anticuerpo policlonal que reconoce la proteína P nativa en células infectadas con el virus de la rabia.

Factor estimulante de colonias de granulocitos en pacientes con cáncer Granulocyte-colony stimulating factor in patients with cancer

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María Cristina Céspedes Quevedo

2013-01-01

Full Text Available Se efectuó un estudio descriptivo, longitudinal y prospectivo de 26 pacientes con cáncer en diferentes localizaciones asociado a leucopenia y neutropenia inducidas por citotóxicos, atendidos en el Servicio de Quimioterapia del Hospital Oncológico Docente "Conrado Benítez" de Santiago de Cuba, de mayo del 2011 a igual mes del 2012, con vistas a determinar el efecto del factor de colonias granulocítica recombinante Ior® LeukoCIM --producido por el Centro de Inmunología Molecular de Ciudad de La Habana-- en ellos mediante la realización de conteos globales de leucocitos y neutrófilos, antes y después de aplicar el tratamiento. En la serie predominaron el sexo femenino, el cáncer de mama y el estadio clínico II; también se obtuvo que 92,3 % de los pacientes respondieron satisfactoriamente a la terapia, el estadio clínico del cáncer no modificó el efecto mielodepresor de los citotóxicos ni el mieloestimulador de la hormona, y el cisplatino y la adriamicina se relacionaron con las neutropenias mayores y la falta de reacción al factor. Para finalizar, el Ior® LeukoCIM estimuló el sistema granulopoyético de la mayoría de los afectados.A descriptive, longitudinal and prospective study was conducted in 26 patients with cancer in different locations associated with leukopenia and neutropenia induced by cytotoxic drugs, treated at the Chemotherapy Department of "Conrado Benítez" Teaching Oncology Hospital of Santiago de Cuba, from May 2011 to the same month of 2012, with the purpose of determining the effect of the recombinant granulocyte-colony factor Ior® LeukoCIM --produced by the Center of Molecular Immunology in Havana city-- in them by means of global counts of leukocytes and neutrophils before and after applying the treatment. Female sex, breast cancer and clinical stage II prevailed in the series. It was also found that 92.3% of patients responded successfully to the therapy, the clinical stage of cancer did not modify the

Inmunoterapia en la Artritis Reumatoidea

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Virginia Torres

1999-02-01

Full Text Available La inmunoterapia en la artritis reumatoidea incluye el uso de moléculas producidas por células del sistema inmune, o que participan en reacciones inflamatorias así como formas recombinantes de dichas moléculas. El desarrollo de anticuerpos monoclonales condujo al ensayo de terapias anticélulas T sin resultados alentadores. El tratamiento con anticuerpos monoclonales antifactor de necrosis tumoral alfa resulta prometedor actualmente; así como el uso de citokinas recombinantes que condicionen el predominio de células T cooperadoras tipo 2. Sin embargo, en el futuro el uso de la terapia génica podría ser el arma más poderosa para el tratamiento de la artritis reumatoideaThe immunotherapy in the rheumatoid arthritis includes the use of molecules produced by cells of the immune system or that take part in inflammatory reactions as well as recombinant forms of such molecules. The development of monoclonal antibodies led to the trial of anti T cell therapies without encouraging results. The treatment with anti-tumor necrosis factor alpha monoclonal antibodies is promising at present, as well as the use of recombinant citokines that condition the predominance of type II helper-T-cells. However, in the future the use of gene therapy could be the most powerful weapon to treat rheumatoid arthritis

Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity

DEFF Research Database (Denmark)

Bjelke, Jais R; Olsen, Ole H; Fodje, Michel

2008-01-01

between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity. Moreover, mutation of the Lys(161)-interactive residue Asp(217) or Asp(219) to Ala reduced the amidolytic...... activity by 40-50%, whereas the K161A mutation resulted in 80% reduction. Hence one of these Asp residues in the Ca(2+)-binding loop appears to suffice for some residual interaction with Lys(161), whereas the more severe effect upon replacement of Lys(161) is due to abrogation of the interaction with the N......-terminal tail. However, Ca(2+) attenuation of the repulsion between Asp(212) and Glu(296) keeps the activity above that of apoFVIIa. Altogether, our data suggest that repulsion involving Asp(212) in the Ca(2+)-binding loop suppresses FVIIa activity and that optimal activity requires a favorable interaction...

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

Science.gov (United States)

Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

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Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

2016-01-01

Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

Caracterização da imunogenicidade das proteínas recombinantes Virb9, Virb10 e fator termo instável de Elongação de Peptídeos de Anaplasma marginale em camundongos

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Ana Beatriz Canevari Castelão

2012-10-01

Full Text Available Considerando as limitações dos atuais métodos de controle contra a anaplasmose bovina, o desenvolvimento de uma vacina efetiva se faz necessário. A partir do advento da análise genômica e proteômica, novas proteínas de membrana de Anaplasma marginale foram identificadas como possíveis candidatas a componentes de uma vacina, tais como, VirB9,VirB10 e Fator Termo Instavél de Elongação de Peptídeos (EF-Tu. Embora estas proteínas ainda não estejam bem caracterizadas na membrana de A. marginale, a produção destas na forma recombinante (rVirB 9, rVirB10 e rEF-Tutem sido realizada, mas as mesmas ainda não foram exploradas em formulações vacinais. Neste trabalho, avaliou-se ouso de rVirB9, rVirB10 e rEF-Tu emulsionadas em adjuvante Montanide em camundongos. Nas condições testadas, verificou-se a indução de forte resposta imune humoral com a produção de IgG1 e IgG2a, sendo que as proporções dos níveis de produção destas subclasses indicam predomínio de IgG1. Entretanto, esplenócitos de animais, que foram injetados com rVirB9 ou rVirB10, produziram interferon-gama acima do limite de detecção do ensaio após estimulação in vitro, sinalizando assim resposta celular específica. Assim, novas avaliações serão realizadas com a finalidade de modular o perfil de resposta imune obtido em bovinos e avaliar a proteção contra A. marginale.

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats A administração exógena de leptina recombinante induz à angiogênese em queimaduras cutâneas provocadas em ratos

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Ioannis Liapakis

2008-04-01

Full Text Available BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels. PURPOSE: The effect of exogenously administered leptin on the healing process of a full tissue burn wound model. METHODS: Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C. For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1, in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant

Factores asociados a una respuesta inadecuada a la vacunación contra la hepatitis B en personal sanitario

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Tolosa Martínez Natividad

1998-01-01

Full Text Available FUNDAMENTO: La vacuna recombinante contra la hepatitis B confiere inmunidad aproximadamente en el 95 % de los casos, pero existe un porcentaje que responde insuficientemente. El objetivo de este trabajo es evaluar los factores que se asocian con una inadecuada respuesta inmunitaria. MÉTODOS: Se trata de un estudio observacional y analítico en el que se sigue retrospectivamente una cohorte de sujetos vacunados frente al virus de la hepatitis B (VHB. Se recogieron las variables de interés del personal sanitario que cumplía los criterios de inclusión, del Área de Salud 9 de la Comunidad Valenciana (n=827. Tras la vacunación se determinó la titulación de anticuerpos de superficie (antiHBs para comprobar la respuesta, considerándose niveles protectores los superiores a 10 mUI/ml. RESULTADOS: Se produjo una adecuada seroconversión en el 94,4% de los vacunados. La baja o nula respuesta a la vacuna se asoció significativamente y de forma independiente con variables como el sexo masculino, la edad, el índice de masa corporal (IMC y el tabaquismo. El consumo de alcohol y los niveles de GPT, aunque no se relacionaron de forma significativa con la respuesta a la vacuna, actuaron como posibles factores de confusión. CONCLUSIONES: La inmunogenicidad de la vacuna es satisfactoria. Es importante cuantificar los niveles de antiHBs, sobretodo cuando hay factores predictivos de mala respuesta. De esta manera, es posible identificar a aquellos que precisan dosis de recuerdo y a los no respondedores, evitándose así situaciones de falsa sensación de protección frente al VHB.

Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

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Sara P. Y. Che

2017-11-01

Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

Genética molecular de caracteres cuantitativos en cruzamientos dialélicos de tomate

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Guillermo Raúl Pratta

2011-05-01

Full Text Available El objetivo de este trabajo fue evaluar marcadores moleculares y caracteres cuantitativos en un cruzamiento dialélico completo sin recíprocos, entre cinco líneas recombinantes de tomate y sus híbridos. Se obtuvieron perfiles de AFLP ("amplified fragment length polymorphism" y de polipéptidos del pericarpio en cuatro estados de madurez del fruto de 15 genotipos. Se evaluaron, entre otros: peso, acidez titulable, pH, vida poscosecha y firmeza. Se calculó el porcentaje de polimorfismo para los marcadores moleculares y el porcentaje de variabilidad genética para los caracteres cuantitativos en el grupo de líneas recombinantes, el de híbridos y el conjunto de genotipos. Se realizaron análisis de agrupamiento con cada nivel de variación genética. Para AFLP, el porcentaje de polimorfismo varió entre 34 y 54% y, para los perfiles polipeptídicos, entre 40 y 78%. Mayor polimorfismo fue observado en el grupo de híbridos. La variabilidad genética fue de 100% para acidez y 34% para firmeza, con los mayores valores en los parentales. La similitud genética varió entre los genotipos según el nivel de variación genética; pero la consistencia en el agrupamiento de algunas líneas recombinantes y sus híbridos fue conservada, lo que evidenció asociaciones entre los datos moleculares y fenotípicos.

Experiencia con las reacciones adversas asociadas con el interferón alfa 2b recombinante en hematología Experience with the adverse reactions associated with recombinant alpha 2b interferon in hematology

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Idalmis Brito Pascual

2005-08-01

Full Text Available El interferón alfa 2b es una citoquina con actividad antiviral, antiproliferativa e inmunomoduladora que ha demostrado ser eficaz para el tratamiento de enfermedades virales y neoplásicas. El presente trabajo se realizó con el propósito de describir la frecuencia de las reacciones adversas asociada con la administración de Heberon alfa R (interferón alfa 2b recombinante en enfermedades hematológicas. Se analizaron las características de base de los pacientes, así como la frecuencia, intensidad y relación de causalidad de los eventos reportados. Los eventos adversos más frecuentes fueron las manifestaciones del síndrome gripal que incluyó fiebre, escalofrío, astenia, mialgias, anorexia y cefalea. Estas manifestaciones son transitorias y responden al tratamiento con antiinflamatorios no esteroideos. La mayoría de los eventos fueron de intensidad leve a moderada y no requirieron la suspensión del tratamiento. En conclusión, el Heberon alfa R es un fármaco relativamente seguro para el tratamiento de trastornos hematológicosAlpha 2b interferon is a cytokine with antiviral, antiproliferative and immunomodulator activity that has proved to be efficient for the treatment of viral and neoplastic diseases, This paper is aimed at describing the frequency of adverse reactions associated with the administration of alpha R Heberon (recombinant alpha 2b interferon in hematological diseases. The basic characteristics of the patients, as well as the frequency, intensity and causality relation of the reported events were analyzed. The most common adverse effects were the manifestations of the gripal syndrome that included fever, chills, astenia, myalgia, anorexia and headache. These manifestations are transitory and respond to the treatment with non-steroideal antiinflammatory drugs. Most of the events were from mild to moderate intensity and did not require the suspension of the treatment. To conclude, alpha R Heberon is a relatively safe drug

Emergency caesarean delivery in a patient with cerebral malaria-leptospira co infection: Anaesthetic and critical care considerations

Directory of Open Access Journals (Sweden)

Sukhen Samanta

2014-01-01

Full Text Available Malaria-leptospira co-infection is rarely detected. Emergency surgery in such patients has not been reported. We describe such a case of a 24-year-old primigravida at term pregnancy posted for emergency caesarean delivery who developed pulmonary haemorrhage, acute respiratory distress syndrome, acute kidney injury, and cerebral oedema. Here, we discuss the perioperative management, pain management (with transverse abdominis plane block, intensive care management (special reference to management of pulmonary haemorrhage with intra pulmonary factor VIIa and the role of plasmapheresis in leptospira related jaundice with renal failure.

Comparison of two recombinant hepatitis B vaccines and their interchangeability in Argentine infants Comparación de dos vacunas recombinantes contra la hepatitis B y su intercambiabilidad en lactantes argentinos

Directory of Open Access Journals (Sweden)

Miguel Tregnaghi

2004-01-01

-B.OBJETIVO: Comparar dos vacunas pediátricas recombinantes contra la hepatitis B -Euvax-B y la vacuna de referencia Engerix-B- en cuanto a su inmunogenicidad y reactogenicidad, e investigar su intercambiabilidad, es decir, si el esquema de vacunación contra la hepatitis B de tres dosis comenzado con una primera dosis de Engerix-B puede completarse con dos dosis de Euvax-B. MÉTODOS: Este estudio se llevó a cabo en la ciudad de Córdoba, Argentina, entre marzo de 1999 y febrero de 2000. Se vacunó contra la hepatitis B a tres grupos de 100 lactantes argentinos a los 0, 1 y 6 meses de edad. El grupo A recibió tres dosis de Euvax-B; el grupo B, tres dosis de Engerix-B; y el grupo C, una dosis de Engerix-B seguida de dos dosis de Euvax-B. Para evaluar la reactogenicidad se utilizó la información brindada por los padres acerca de determinados fenómenos locales o sistémicos solicitados por los investigadores que hubieran ocurrido durante los siete días posteriores a la vacunación. Para establecer si eran idénticas clínicamente las vacunas Euvax-B y Engerix-B se utilizaron las tasas de seroprotección -es decir, títulos de anticuerpos contra el antígeno de superficie de hepatitis B (anti-HBsAg > 10 miliunidades internacionales por mililitro (mUI/mL- alcanzados dos meses después de la tercera dosis. RESULTADOS: La reactogenicidad fue baja en los tres grupos de estudio. A los 5 meses de la segunda dosis (es decir, inmediatamente antes de la tercera dosis, las tasas de seroprotección fueron 95,9%, 94,7% y 90,2% en los grupos A, B y C, respectivamente. Dos meses después de la tercera dosis, todos los lactantes se encontraban protegidos, con concentraciones medias geométricas de anti-HBsAg de 2 468,1 mUI/mL en el grupo A, de 1 714,8 mUI/mL en el grupo B y de 2 075,3 mUI/mL en el grupo C. CONCLUSIONES: Las dos vacunas recombinantes contra la hepatitis B estudiadas fueron bien toleradas y altamente inmunogénicas. La vacuna Euvax-B fue clínicamente idéntica (no inferior a la

Korruptsiooni bioloogilised juured / Jaak Rebane

Index Scriptorium Estoniae

Rebane, Jaak

1999-01-01

Kuritarvitusele aitavad viia inimese teatud omadused, nagu egoism, piiratus, ahnus, jultumus, tarbimismentaliteet, tõusiklikkus. Korrumptantsaab varumistungi ajel ebaeetilisest käitumisest hoopis positiivse emotsiooni

Insurance bankruptcy creates political storm

Index Scriptorium Estoniae

2005-01-01

Hoolimata peaminister Algirdas Brazauskase nõudmisest, keeldus Leedu kindlustusinspektsiooni juht Edvinas Vasilis-Vasiliauskas oma kohalt tagasi astumast, kuna soovib viia lõpule kindlustusseltsi Ingo Baltic pankrotiprotsessi

Gaza võitmatu armaada / Andres Laasik

Index Scriptorium Estoniae

Laasik, Andres, 1960-2016

2010-01-01

Katsest viia laevadega humanitaarabi Gaza sektorisse. Autor on arvamusel, et kui Vabaduse laevastik ongi saavutanud soovitu ja murdnud blokaadi, siis uus tasakaal pole julgeoleku mõttes sugugi kindlam

Caracterización e inmunoreactividad de la proteína acídica Ribosomal P2ß de L. (V. braziliensis

Directory of Open Access Journals (Sweden)

Carlos Padilla R

2003-04-01

Full Text Available Introducción: El diagnóstico serológico de la leishmaniasis usando proteínas totales presenta reacciones cruzadas. La caracterización de nuevos antígenos de Leishmania mejorará el uso de herramientas serológicas en el diagnóstico de esta enfermedad. Objetivo: Caracterizar un nuevo antígeno de Leishmania. Materiales y métodos: Se seleccionó el bacteriófago T166-U19 de una biblioteca de cADN de L. (V. braziliensis el cual es reactivo a mezclas de sueros de leishmaniasis cutánea y mucocutánea. El cADN del clon T166-U19 fue subclonado en el plásmido pGEX, luego secuenciado y la proteína recombinante fue expresada. La reactividad de esta proteína recombinante se evaluó por ELISA. Resultados: El cADN del clon T166- U19 presentó un marco de lectura abierto de 318 pb que traduce una proteína de 105 aminoácidos con 81,1%, 82,9% y 60,7% de identidad total con la proteína acídica ribosomal LiP de L. (L. infantum, P2 de L. (L. donovani, y P2 de T. cruzi, respectivamente. Además, la proteína recombinante presentó baja reactividad (50% con sueros de pacientes con leishmaniosis, mientras que presentó reactividad cruzada con sueros de pacientes chagásicos. Conclusiones: Se caracterizó por primera vez la proteína acídica ribosomal P2B de L. (V. braziliensis, y presentando baja reactividad con sueros de pacientes con leishmaniasis.

Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

International Nuclear Information System (INIS)

Cocco, Emiliano; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Pecorelli, Sergio; Lockwood, Charles J; Santin, Alessandro D; Varughese, Joyce; Buza, Natalia; Bellone, Stefania; Glasgow, Michelle; Bellone, Marta; Todeschini, Paola; Carrara, Luisa; Silasi, Dan-Arin

2011-01-01

Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology. Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated the in vitro expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs- 51 chromium-release-assays against cervical cancer cell lines in vitro. Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p = 0.0023 qRT-PCR; p = 0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%, p < 0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (p = 0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (p = 0.597). TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell

Veemajandus saab jõudsalt areneda / Aare Lepaste

Index Scriptorium Estoniae

Lepaste, Aare, 1970-

2004-01-01

8. detsembril kirjutasid seitsme vee-ettevõtte esindajad, KIK-i juhataja ja keskkonnaminister alla Eesti suurimale keskkonnaprojektile. Projekti eesmärk on viia omavalitsuste veemajanduse infrastruktuur vastavusse EL-i direktiividega.

Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

Science.gov (United States)

Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

2018-05-10

Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

Iisraeli ühiskond on lõhenemas / Jüri Piirisild

Index Scriptorium Estoniae

Piirisild, Jüri

2004-01-01

Iisraeli sisepinged seoses juhtkonna plaaniga juudi asunikud Gaza sektorist välja viia ning aastakümneid kestnud konflikt palestiinlastega on mõjutanud nii riigi majandust kui usaldust peaminister Ariel Sharoni vastu

Tissue- and Condition-Specific Isoforms of Mammalian Cytochrome c Oxidase Subunits: From Function to Human Disease

Directory of Open Access Journals (Sweden)

Christopher A. Sinkler

2017-01-01

Full Text Available Cytochrome c oxidase (COX is the terminal enzyme of the electron transport chain and catalyzes the transfer of electrons from cytochrome c to oxygen. COX consists of 14 subunits, three and eleven encoded, respectively, by the mitochondrial and nuclear DNA. Tissue- and condition-specific isoforms have only been reported for COX but not for the other oxidative phosphorylation complexes, suggesting a fundamental requirement to fine-tune and regulate the essentially irreversible reaction catalyzed by COX. This article briefly discusses the assembly of COX in mammals and then reviews the functions of the six nuclear-encoded COX subunits that are expressed as isoforms in specialized tissues including those of the liver, heart and skeletal muscle, lung, and testes: COX IV-1, COX IV-2, NDUFA4, NDUFA4L2, COX VIaL, COX VIaH, COX VIb-1, COX VIb-2, COX VIIaH, COX VIIaL, COX VIIaR, COX VIIIH/L, and COX VIII-3. We propose a model in which the isoforms mediate the interconnected regulation of COX by (1 adjusting basal enzyme activity to mitochondrial capacity of a given tissue; (2 allosteric regulation to adjust energy production to need; (3 altering proton pumping efficiency under certain conditions, contributing to thermogenesis; (4 providing a platform for tissue-specific signaling; (5 stabilizing the COX dimer; and (6 modulating supercomplex formation.

77 FR 61753 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Science.gov (United States)

2012-10-11

.... 20121302 G Arrow Electronics. Inc.; John F. Baker (Micro Electronics, Inc.); Arrow Electronics, Inc. 20121303 G Wind Point Partners L.P.; Mistral Equity Partners, LP; Wind Point Partners VII-A, L.P. 20121307...

Lennufirmad ägavad nafta hinna surve all / Tõnis Arnover

Index Scriptorium Estoniae

Arnover, Tõnis, 1952-

2004-01-01

Nafta kõrge hind ähvardab palju kütust tarbivad lennukompaniid kahjumisse viia kuna tiheda konkurentsi tingimustes piletihindu tõsta ei soovita. Diagramm: Nafta hind tänavu kerkinud üle kolmandiku

Aeg panustada nafta hinna langusele / Tarvo Vaarmets

Index Scriptorium Estoniae

Vaarmets, Tarvo

2008-01-01

Autor analüüsib maailma naftatootmist ning leiab, et vähenev naftanõudlus võib viia nafta hinna langusele. Vt. samas: Kuidas nafta hinna langusest kasu lõigata?; Tabel: Naftaturg; Võrdlusandmed

Laurentiuse kirik päästab Saueri oreli osi niiskuse käest / Andres Sepp ; kommenteerinud Anti Toplaan

Index Scriptorium Estoniae

Sepp, Andres, 1976-

2009-01-01

Kuressaare Laurentiuse kiriku kogudus otsib võimalusi viia 1881. a. Wilhelm Saueri firmas valminud vanima Eestis säilinud oreli puidust ja metallist osad kuivemasse kohta. Praegu seisavad need kiriku garaažis

Savisaar : palk nelja aasta pärast 25 000 krooni / Kadi Heinsalu

Index Scriptorium Estoniae

Heinsalu, Kadi, 1966-

2006-01-01

Ilmunud ka: Delovõje Vedomosti 20. sept. lk. 6. Keskerakonna eesmärgiks on viia keskmine palk Eestis järgmise nelja aastaga 25 000 kroonini - Euroopa Liidu keskmisele tasemele. Diagramm: Palk avalikus sektoris

Las pank tuleb kiiresti kliendi juurde / Vallo Toomet

Index Scriptorium Estoniae

Toomet, Vallo, 1960-

2005-01-01

Autor on seisukohal, et pank võiks ise otsida klienti, kellele teha laenupakkumine, ning selgitab, kuidas seda ideed ellu viia. Sama süsteem võiks kehtida ka innovatsioonis, riskiprojektide puhul ja ettevõtluses

WW instituudi direktor Christopher Flavin : Kyoto protokoll viiakse ellu Bushita / Christopher Flavin ; interv. Tarmo Virki

Index Scriptorium Estoniae

Flavin, Christopher

2002-01-01

World Watch Instituudi direktor leiab, et maailm vajaks globaalset keskkonnaorganisatsiooni, mis tasakaalustaks Maailma Kaubandusorganisatsiooni mõju. Euroopa Liit ja Jaapan suudavad Kyoto protokolli ratifitseerimise ellu viia ka ilma USA-ta. Lisa: Tuumaenergia pole lahendus

Omavalitsused küsivad kohustuste täitmiseks riigilt raha juurde / Harda Roosna

Index Scriptorium Estoniae

Roosna, Harda, 1956-

2005-01-01

Läbirääkimistel valitsustega taotlevad omavalitsusliidud, Eesti Maaomavalitsuste liit (EMOL) ja Eesti Linnade liit (ELL), riigilt tulevaseks riigieelarve planeerimisperioodiks (2006-2009) kohalike omavalitsuste tulude kasvu, et viia tulubaas vastavusse omavalitsustele pandud kohustustega

Efeito da utilização da somatotropina bovina recombinante (bST sobre a produção de leite em búfalas Effect of recombinant bovine somatotropin (bST utilization on milk production from buffaloes

Directory of Open Access Journals (Sweden)

André Mendes Jorge

2002-06-01

Full Text Available O objetivo deste trabalho foi estudar o resultado da utilização da somatotropina bovina recombinante (bST atuando na produção de leite em búfalas da raça Murrah. Empregaram-se 28 búfalas multíparas da raça Murrah, divididas em dois grupos homogêneos de 14 animais, recebendo os seguintes tratamentos: Grupo 1 ¾ Controle (solução salina e Grupo 2 ¾ 500 mg de bST/cabeça a cada 14 dias, durante 7 meses. Búfalas tratadas com bST exibiram incrementos de 48,52%, 32,80% e 32,80% nas produções total de leite, corrigida, depois, para 4% de gordura e média diária, respectivamente. A somatotropina elevou a produção total de gordura sem alterar a porcentagem dela no leite. A administração de bST não afetou a porcentagem de proteína do leite todavia, a produção total de proteína foi aumentada. Quanto à duração da lactação, o tratamento com bST diferiu do controle, o que demonstra a maior persistência da lactação de búfalas tratadas com bST.The objective of this work was to study the effect of recombinant bovine somatotropin (bST utilization on milk production from Murrah buffaloes. Twenty eight multiparous Murrah buffaloes were used and divided into two homogeneous groups of 14 animals, receiving the following treatments: Group 1 ¾ Control (salt solution and Group 2 ¾ 500 mg of bST/head every 14 days during 7 months. Buffaloes treated with bST presented increase of 48.52%, 32.80% and 32.80% on total milk yield, adjusted to 4% of fat and average daily milk yield, respectively. Somatotropin increased total fat milk yield without alter fat percentage of milk. Administration of bST did not affect protein percentage of milk while total protein milk yield increased. As for the lactating period, the treatment with bST differed of the control, what might have denoted in larger persistence of the lactation from buffaloes treated with bST.

THE APPLICATION OF RECIPROCAL TEACHING METHOD FOR IMPROVING THE UNDERSTANDING OF MATHEMATICS CONCEPT OF 7TH GRADE STUDENTS SMP NEGERI 2 DEPOK.

Directory of Open Access Journals (Sweden)

Tatag Bagus Argikas

2016-10-01

Full Text Available This research aims to: (1 describe the implementation of learning mathematics with Reciprocal Teaching methods that is for improving the concept of learning understanding mathematic in class VIIA SMP Negeri 2 Depok. (2 Knowing the increased understanding of student learning in class VIIA SMP Negeri 2 Depok use Reciprocal Teaching methods. This research constitutes an action in class that is according along the teacher. The data of research was collated by sheet observations and each evaluation of cycles. That is done in two cycles. The first was retrieved the average value of student learning achievement of 70.96%. The second was retrieved achievement of 90.32%. Thus this learning model can increase student learning understanding.   Key word: The understanding of Mathematical Concept, Reciprocal Teaching Method.

Börs nutab taga Eesti Energia loobumist / Jaana Pikalev ; kommenteerinud Jürgen Ligi, Sandor Liive

Index Scriptorium Estoniae

Pikalev, Jaana

2010-01-01

SEB privaatpanganduse osakonna strateeg Peeter Koppel, LHV Panga analüütik Sten Pisang, investor Stefan Andresson avaldavad arvamust seoses otsusega Eesti Energia veel mitte börsile viia. Majandus- ja kommunikatsiooniminister Juhan Partsi arvamus

Ingliskeelne eesti luule ja glokaalsuse keskenduvad keerud / Lauri Pilter

Index Scriptorium Estoniae

Pilter, Lauri, 1971-

2010-01-01

Inglise keele rollist eesti luuleteadvuses üldiselt, Bernard Kangro kogust "Earthbound" (1951) kui esimesest ingliskeelsest eesti luuletaja valikkogust ning võimalikest järeldustest, milleni võiks viia metafooride võrdlev uurimine eesti ja inglise luules

Üks küsimus

Index Scriptorium Estoniae

2003-01-01

Euroopa Komisjoni laienemisvoliniku Günther Verheugeni eestkõneleja Jean-Christophe Filori vastab küsimusele, milleni võivad viia valitsuskriisist tulenevad häired Riigikogu töös EL-iga liitumiseks vajalike seaduste vastuvõtmisel

Eesti üldhariduse finantsreformi olemus ja probleemid / Janno Reiljan, Ele Reiljan

Index Scriptorium Estoniae

Reiljan, Janno, 1951-2018

2005-01-01

Läbiviidav reform võib täiendavate investeerimisvahendite eraldamisest hoolimata kohalikele omavalitsustele pandavate pikaajaliste võlakohustuste ja õpikulude kaasrahastamise kohustuse koosmõjul üldhariduse koolivõrgu regionaalse tasakaalustamise asemel senisest enam tasakaalust välja viia

Investor wants listing for Estonian Railway, state officials balk at prospect

Index Scriptorium Estoniae

2004-01-01

Eesti Raudtee suuromanik Baltic Rail Service tahab ettevõtte 2005. aasta keskpaigaks börsile viia. Riik, mis on firma vähemusaktsionär, pole plaaniga nõus, kuna BRS-il on täitmata investeerimiskohustused

Üürilepingu erakorraline ülesütlemine üürniku makseviivituse tõttu / Kaidi Urgas, Karin Sein

Index Scriptorium Estoniae

Urgas, Kaidi, 1989-

2013-01-01

Võlaõigusseaduse § 316 kohaldamise teoreetilistest alustest ja rakendamise praktikast Eesti kohtutes ning seaduse ajakohastamise vajadusest, et poolte õigused ja kohustused paremini tasakaalu viia. Üürileandja ülesütlemisõigus Šveitsi ja Saksa õiguses

Human Recombinant Factor VIIa is Neuroprotective in a Model of Traumatic Brain Injury and Secondary Hypoxemia

National Research Council Canada - National Science Library

Bauman, R. A; Long, J. B; Ketchum, L. H; Macdonald, V. W

2004-01-01

.... In the untraumatized brain, TF is physically isolated from FVII. However, traumatic brain injury (TBI) frequently results in the disruption of the vascular endothelium and resultant exposure of FVII to subendothelial TF...

Off-label use of recombinant factor VIIa for treatment of haemorrhage: results from randomized clinical trials

DEFF Research Database (Denmark)

Johansson, Per Ingemar

2008-01-01

) for evidence of such an approach. Methods In October 2007, a review of RCT involving rFVIIa for non-haemophilic indications was performed. The effect of rFVIIa on blood loss and transfusion requirements was recorded. Results Seventeen RCTs were identified concerning different bleeding conditions, for example......, secondary to surgery, infection and stem cell transplantation. Three pilot studies reported a significant reduction in transfusion requirements and/or blood loss in the rFVIIa-treated groups, but these have not been confirmed in large randomized trials. No difference in thromboembolic complications between...

Fremantle Media ekspordib seriaale kogu maailma / Andrew Edgecliffe-Johnson ; tõlk. Erik Aru

Index Scriptorium Estoniae

Edgecliffe-Johnson, Andrew

2007-01-01

Teleproduktsioonifirmast Fremantle Media. Saateformaatide eksportimisel saavutatud edu teeb firmast õpikunäite, kuidas viia tooteid üle maailma, muutes neid just piisavalt, et sobida kohaliku maitsega, jäädes samas truuks algideele. Edu ei vaja tõlget

Piirivalve saab 147 miljoni eest uhke helikopteri / Sigrid Laev

Index Scriptorium Estoniae

Laev, Sigrid

2005-01-01

Eesti piirivalve saab helikopteri Agusta Bell, kopteri soetamine täidab Schnegen Facility programmi eesmärki, mille kohaselt tuleb EL-i välispiiride valve viia vastavusse Schengeni õigusruumi nõuetega. Raha ostmiseks annab abiprogramm Schengen Facility

Over my dead body / Martin Kala

Index Scriptorium Estoniae

Kala, Martin, 1977-

2004-01-01

Arutlus Türgi võimalikust liitumisest Euroopa Liiduga. Autori hinnangul on Türgi tõestanud oma suutlikkust viia läbi järjepidevaid reforme ja Euroopasse sobivad kõik riigid, mis suudavad tõestada oma demokraatlikku elukorraldust

Ettevaatust, kaitsepolitsei! / Roy Strider

Index Scriptorium Estoniae

Strider, Roy, 1974-

2007-01-01

Ajendatuna anarhistliku liikumise PunaMust meeleavalduse jälgimisest end ajakirjanikuks nimetanud kaitsepolitsei töötaja poolt kirjutab autor kaitsepolitsei mõttetust nuhkimisest oma kodanike järele, mis võib viia jälgimisühiskonnani

Kuidas puutuvad ring, kolmnurk ja ruut lillepeenrasse? / Ülle Kikas, Terje Hõim

Index Scriptorium Estoniae

Kikas, Ülle, 1949-

2016-01-01

2012. aastal alustas haridus- ja teadusministeerium koostöös Tartu Ülikooli ja tarkvara tootva Wolframi konsortsiumiga arvutipõhise statistika arendusprojekti, et viia statistika õpetamine koolides vastavusse tänapäeva võimaluste ja nõudmistega

The coagulopathy in sepsis: significance and implications for treatment

Directory of Open Access Journals (Sweden)

Berardino Pollio

2011-09-01

Full Text Available Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC. There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

Mysterious bruises

Directory of Open Access Journals (Sweden)

H Chen

2012-01-01

Full Text Available A 69-year-old man presented with multiple spontaneous bruises in the past 2 weeks. Several large-sized hematomas were found on examination. The initial investigation revealed a prolonged activated partial thromboplastin time (aPTT with normal platelet count and international normalized ratio. Further investigation revealed a low factor VIII activity secondary to presence of factor VIII inhibitor, making the diagnosis of acquired hemophilia A. Further work-up revealed that pernicious anemia was present and acted as an associated disease. After steroids therapy, his aPTT was normalized and the factor VIII inhibitor titer became undetectable. 2 months later, a relapse occurred and new hematomas appeared at his retropharyngeal space and left arm. His bleeding was controlled by administration of recombinant factor VIIa, and a combined therapy of intravenous steroids and rituximab was given to eradicate the inhibitor. The approach to workup of bleeding disorders as well as treatment of acquired hemophilia A are herein discussed.

Multiple roles of the coagulation protease cascade during virus infection.

Science.gov (United States)

Antoniak, Silvio; Mackman, Nigel

2014-04-24

The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

Investor kardab ebakindlust / Aigar Ojaots

Index Scriptorium Estoniae

Ojaots, Aigar, 1974-

2007-01-01

ÜRO eriraportööri Jean Ziegleri avaldus kehtestada biokütuse kasutamisele viieks aastaks moratoorium võib viia olukorrani, kus keegi ei julge investeerida uutesse tehnoloogiatesse, kuna 5 aasta pärast võidakse taas meelt muuta

Vertikal bez granits / Svetlana Ragrina

Index Scriptorium Estoniae

Ragrina, Svetlana

2004-01-01

Moskva elab sõjaaja reaalsuses, terroriaktid ja terrorismioht võimaldavad võimuorganitel sisse viia kodanike kaitseks täiendavaid vabaduste ning õiguste piiranguid. Venemaa president Vladimir Putin tutvustas valitsusele, föderatsiooni subjektidele ja rahvale kavandatavaid muudatusi riigi juhtimises

Linnahalli renoveerimine venib veel vähemalt aasta / Tuuli Aug

Index Scriptorium Estoniae

Aug, Tuuli

2010-01-01

Tallinna linn ja USA firma Tallinn Entertainment LLC otsustasid Tallinna Linnahalli renoveerimiseks ja seda ümbritsevate kinnistute hoonestamiseks luua ühisettevõtte, mille asutamine ja hoonestusõiguse seadmine loodetakse lõpule viia jaanuaris 2011. Detailplaneeringust ja renoveerimisprojekti koostamisest, ühisfirma ehitusplaanist

Gordon Brown lubab valijal riigieelarvet ümber teha / Siim Trumm

Index Scriptorium Estoniae

Trumm, Siim

2007-01-01

Peaminister Gordon Brown kavandab mitmeid reforme, et viia riigivõim rahvale lähemale. Inglismaa kümne piirkonna inimestele antakse võimalus otsustada rahvahääletuse kaudu kohaliku eelarve jaotamise üle. Lisa: Browni ja leiboristide toetus kasvab

Tere tulemast uude sõtta / Jüri Pino

Index Scriptorium Estoniae

Pino, Jüri, 1970-

2011-01-01

14. aprillil toimunud NATO välisministrite kohtumisel viitas USA riigisekretär Hillary Clinton võimalusele, et Liibüasse tuleb ka maaväed sisse viia. Autor leiab, et see tähendab ka Eestile uue sõja algust

Birma takistab välisabi jagamist / Hendrik Vosman

Index Scriptorium Estoniae

Vosman, Hendrik

2008-01-01

Birma sõjaväediktatuur võtab küll tsüklon Nargise põhjustatud looduskatastroofi tõttu välisabi vastu, kuid keelab abiandjatel seda hädalistele kohale viia. Lisa: Ohvrite arv. Vt. samas: Referendum toimus katastroofist hoolimata

Jiri Shibori konstruktivistlik kujundimaailm / Eilve Manglus

Index Scriptorium Estoniae

Manglus, Eilve, 1977-

2004-01-01

Metallide tehnoloogiat õppinud Jiri Shibori näitus "Ehtekunsti ja skulptuuri vahel" Deco galeriis kuni 10. IV. Personaalnäitus toimub EKA ehte- ja sepakunsti osakonna kutsel, et viia läbi külmkinnituslike konstruktsioonidega metallitöö workshop

Associação entre proteínas do plasma seminal, motilidade e viabilidade espermática em coelhos submetidos a doping genético

Directory of Open Access Journals (Sweden)

G Urtiaga

2013-02-01

Full Text Available Neste trabalho foi estudada a correlação entre o perfil proteico do plasma seminal e a motilidade e viabilidade espermática em coelhos submetidos ao tratamento com vetores de expressão contendo o gene da eritropoetina (EPO e com EPO recombinante humana. Foram identificadas, em coelhos submetidos ao tratamento com vetor de DNA contendo o gene da EPO, duas bandas proteicas associadas a alterações na motilidade espermática - 48kDa à baixa motilidade (P<0,05 e 18kDa à alta motilidade (P<0,05 - e esse fator foi associado a maior viabilidade espermática (P<0,05. Em coelhos submetidos ao tratamento com EPO recombinante, um fator proteico, 63kDa, associou-se à alta motilidade espermática (P<0,05, enquanto dois, 26 e 40kDa, foram associados à alta viabilidade espermática (P<0,05. Esses resultados sugerem que o doping genético pode ocasionar mudanças no perfil proteico do plasma seminal, provocando alterações na motilidade e viabilidade espermática.

Control of severe bleeding episode in case of glanzmann's thrombasthenia refractory to platelet transfusion therapy by administering recombinant

International Nuclear Information System (INIS)

Asim, A.; Khan, B.; Hussain, T.

2009-01-01

Glanzmann's thrombasthenia is an autosomal recessive inherited platelet function defect. Though, quantitatively normal, the aggregation ability of platelets is reduced leading to bleeding episodes requiring transfusion of platelet concentrates. We describe a case of 13-year-old girl who had recurrent episodes of epistaxis since birth and was managed with multiple platelet concentrate transfusions and recently admitted with severe epistaxis refractory to platelet transfusion. At this stage administration of recombinant activated factor VII (fVIIa) was considered, which was initially given at 90 mu g/kg dose with little control of bleeding but subsequent second dose of 120 mu g/kg was administered with excellent response and immediate control of bleeding. (author)

Rationale use of blood and its components in obstetric-gynecological practice

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Shakuntala Chhabra

2014-01-01

Full Text Available Appropriate and rational use of blood/components is essential for ensuring availability for the needy as well as preventing risks of transfusion-transmitted diseases and saving resources. Rational use means providing the right blood or products, in the right quantity, to the right patient and at the right time, bridging demand, and supply gap. The safety, adequacy, and effectiveness can only be achieved if unnecessary transfusions can be prevented. Further, risk can be reduced, but cannot be eliminated completely. Alternative to banked blood, autologous blood donation, normovolemic hemodilution, and intraoperative cell salvage should be considered as possible options. Recombinant factor VIIa is a new adjunct for treatment of massive hemorrhage and should be considered, if available.

Orwelli nimekiri / Mihhail Lotman

Index Scriptorium Estoniae

Lotman, Mihhail, 1952-

2014-01-01

Aleksandr II-le sooritatud atentaadikatsest 1866. aastal. Heinrich Bölli teosest "Katharina Blumi kaotatud au, ehk, Kuidas vägivald võib tekkida ja kuhu välja viia". Senaator Joseph McCarthy'st. George Orwelli poolt Informatsiooniuuringute osakonnale esitatud nimekirjast. Orwelli eluloost

Soomlased teevad silma Eesti toidutööstusele / Silva Männik

Index Scriptorium Estoniae

Männik, Silva, 1974-

2004-01-01

EL-iga liitumise eel plaanivad mitmed Soome ettevõtjad investeerida Eesti toiduainetööstustesse ja viia Eesti tooted Soome turule. Diagrammid: Soomlane sööb üha enam Eesti toitu. Kommenteerivad Joakim Helenius ja Ain Hanschmidt. Lisa: Näiteid soomlaste tehingutest

Vene tagapõhjaga organisatsiooni väärtuste uurimisplaan (Kreenholmi Valduse AS näitel) / Anne Reino

Index Scriptorium Estoniae

Reino, Anne, 1972-

2004-01-01

Uurimus Kreenholmi Valdus AS-i väärtustest on plaanis läbi viia 2004. aasta jooksul ning see on üheks osaks suuremast uuringust, mille eesmärgiks on Eesti organisatsioonide väärtuste võrdlev analüüs

PKN Orlen takes share in Mazeikiu Nafta

Index Scriptorium Estoniae

2007-01-01

Poola naftatöötlejatele kuulub peale ostupakkumist väikeaktsionäridele 89% Mazeikiu Nafta aktsiatest, mis võib viia ettevõtte väljaviimiseni börsilt. Jukose väitel pole PKN Orleni raha aktsiate eest endise omanikuni jõudnud

Rein Einasto : Eestis valitud ameerikalik valitsemise tee viib meid katastroofini / Rein Einasto ; interv. Kristi Leppik

Index Scriptorium Estoniae

Einasto, Rein, 1934-

2008-01-01

Kodanikuühiskonna edendamisest Eestis. Aasta missiooniinimese kandidaadiks esitatud professor Rein Einasto arvates päästaks meid avar mõtlemine, et viia inimkond tervikuna teisele teele. Praegune vaba turumajandus on pillamisele, raiskamisele ja kulutamisele üles ehitatud ummiktee. Lisa: Rein Einasto

Miks Ida-Euroopa reformidest väsis / Stefan Wagstyl, Christopher Condon ; tõlk. Erik Aru

Index Scriptorium Estoniae

Wagstyl, Stefan

2006-01-01

Ungari, Tšehhi, Poola, Slovakkia sisepoliitilisest olukorrast. Autorite sõnul on kõikjal piirkonnas langenud eurotsooniga liitumise kavad poliitika ohvriks; majandusteadlaste väitel jätab Kesk-Euroopa kasutamata võimaluse läbi viia uuendusi, mida peab hiljem niikuinii tegema

Construcción de un vector de expresión derivado de virus adenoasociados para corregir in vitro el defecto genético de la enfermedad de Morquio A

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Luis Alejandro Barrera

2008-09-01

Full Text Available Introducción. La mucopolisacaridosis IV A (Morquio A es una enfermedad de depósito lisosómico causada por la deficiencia en la actividad de la enzima N-acetil-galactosamina- 6-sulfato-sulfatasa que produce la acumulación intralisosómica de queratán y condroitín-6-sulfato. Hasta el momento, su manejo es paliativo, por lo que las investigaciones se han enfocado en establecer una terapia que pueda aplicarse tempranamente y garantice la expresión estable de la enzima. En este sentido, la terapia génica se presenta como una de las potenciales alternativas terapéuticas para corregir el defecto genético en la mucopolisacaridosis IV A. Objetivo. Construir vectores de expresión derivados de virus adenoasociados para corregir in vitro la deficiencia enzimática en la mucopolisacaridosis IV A. Materiales y métodos. Se produjeron vectores derivados de virus adenoasociados que portaban el gen humano de la enzima N-acetil-galactosamina-6-sulfato-sulfatasa dirigido por el promotor temprano del citomegalovirus humano, empleando un sistema libre de adenovirus. Se transfectaron células HEK293 y fibroblastos humanos Morquio A con los virus recombinantes, y se determinó la actividad enzimática en el lisado celular a las 24 y 48 horas después de la transfección. Resultados. Se obtuvieron virus adenoasociados recombinantes, libres de adenovirus, con títulos hasta de 2,08 x 1010 cápsides/ml. Tanto en células HEK293 como en fibroblastos Morquio A transfectados, se obtuvieron actividades enzimáticas hasta de 3,05 nmoles/mg por hora, 48 horas después de la transfección. Conclusión. Los virus recombinantes producidos expresaron in vitro la enzima GALNS en las células transfectadas. Estos resultados constituyen el paso inicial para el desarrollo de una terapia génica para la enfermedad de Morquio A empleando vectores derivados de virus adenoasociados.

Distribución de los subtipos del VIH-1 en nueve países de América del Sur, 1995-2002

Directory of Open Access Journals (Sweden)

V. Alberto Laguna-Torres

2005-03-01

Full Text Available Objetivo: Determinar la distribución de los subtipos del virus de la inmunodeficiencia humana (VIH-1 y las presencia de cepas recombinantes en Argentina, Bolivia, Colombia, Chile, Ecuador, Paraguay, Perú, Uruguay y Venezuela a través de estudios epidemiológicos y de genotipificación. Materiales y Métodos: Se incluyeron a los participantes de los protocolos realizados en los nueve paises, incluyendo poblaciones de trabajadoras sexuales (TS, hombres que tienen sexo con hombres (HSH, individuos VIH positivos, gestantes y paciente con tuberculosis (TB. Se utilizó la prueba de movilidad heteroduplex de envoltura (env HMA, ProRT, secuenciamiento completo o ambas para determinar los subtipos de VIH 1. Resultados: Se identificaron 3081 individuos positivos al VIH (de un total de 42 290 voluntarios, las prevalencias oscilaban entre menos de 1% a 29% según población estudiada, siendo mayor en los HSH. Un total de 1654 muestras (54% fueron genotipificadas. Se encontró el subtipo B en 1380 (83% muestras, el subtipo F en 218 (13%, así como los subtipos A y C en 0,1% y 0,4% respectivamente. Se hallaron subtipos recombinantes BF en 39 muestras (2% y formas recombinantes CRF01_AE(0,1%, CRF17_BF(0,4% y CRF02_AG(0,1%. En Venezuela, Colombia, Ecuador, Perú, Bolivia y Chile (paises andinos predominó el subtipo B, mientras en Argentina, Uruguay y Paraguay hubo un alto porcentaje del subtipo F. Conclusiones: En la mayoría de países andinos la epidemia de VIH-1 se concentró en los HSH con un predominio del subtipo B. El subtipo F es más frecuente en las TS en Argentina y Uruguay. Esta información es útil para implementar planes de prevención y futuros ensayos de vacunas en esta región.

Jäätmetega kimpus Estonian Cell annab muda põldudele kompostiks / Ulvar Käärt

Index Scriptorium Estoniae

Käärt, Ulvar, 1982-

2007-01-01

Kundas asuv Estonian Celli tehas jagab ümberkaudsetele talunikele jäätmetest lahtisaamiseks kompostimissegu. Seadused ei sätesta, kuidas Estonian Cellis tekkivaid jäätmeid töödelda. Kommenteerib Peeter Eek: Aasta läbi ei saa muda põllule viia

Pension pool keskmist palka? / Eiki Nestor

Index Scriptorium Estoniae

Nestor, Eiki, 1953-

2007-01-01

Ilmunud ka: Linnaleht : Tartu, 30. okt. 2007, lk. 8. Poliitik, kes lubab viia keskmise pensioni pooleni keskmisest palgast, kuid võõrtööjõudu Eestisse tuua ei taha, pensioniiga ega sotsiaalmaksu tõsta ei soovi, on autori arvates kas rumal või valetab

Vene muuseum hakkab lagunevat hoonet euromiljonitega elustama / Teele Tammeorg

Index Scriptorium Estoniae

Tammeorg, Teele

2010-01-01

Loodav SA Tallinna Vene Muuseum võtab üle MTÜ Vene Muuseum projektid ja saab muuseumihoone kordategemiseks euroraha taotlema hakata. Koidula t. 23 asuva muuseumile rendile antud hoone seisukorrast. Halbade hoiutingimuste tõttu tuli hoonest ära viia kunstikogu. Hoone renoveerimisprojekt valmis 2006. aastal

Kolmas vaatus Euroopa võlakriisis - Portugal. Oht Portugali mainel / Sirje Rank

Index Scriptorium Estoniae

Rank, Sirje, 1966-

2011-01-01

Portugal kavatseb läbi viia riigivõlakirjade emissiooni, samas müüvad teisedki riigid lähiajal võlakirju, mille riskiaste on väiksem. Portugal eitab väidet, nagu oleks Saksamaa ja Prantsusmaa survestanud teda Euroopa kriisifondist abi küsima

Kas missioon on moesõna või organisatsiooni "töövahend"? / Alexander Kotchubei

Index Scriptorium Estoniae

Kotchubei, Alexander, 1963-

2004-01-01

Autor selgitab missiooni olemust, selle sõnastamise vajalikkust organisatsioonis ning arutleb võimalike põhjuste üle, miks missioon ei toimi. Kommenteerivad Marie Edala ja Urmas Kaarlep. Lisa: Sõnumi kujundamiseks vali kahe lähenemise vahel. Vt. samas: Kuidas viia missiooni töötajateni?

"Krengolm" obeshtshajet potesnit Pakistan / Irina Tokareva

Index Scriptorium Estoniae

Tokareva, Irina

2008-01-01

Kreenholmi uue peadirektori Igor Poleshtshuki plaani kohaselt tuleks ettevõtte toodangu müügihinnad viia vastavusse maailmaturu hindadega, alandada tootmise omahinda tellimuste arvu suurendamisega, saada tagasi kaotatud tellijad Euroopast ja leida uusi eelkõige Venemaa turult. Ilmunud ka: Narvskaja Nedelja 13. dets. lk. 3

Illusoorne HIV-vaba Eesti / Nastja Portsjonok

Index Scriptorium Estoniae

Portsjonok, Nastja

2011-01-01

5. juunil 1981 diagnoositi maailmas esimest korda HIV. Eesti on kõige suurema HIV- juhtumite juurdekasvuga riik Euroopa Liidus. Autori hinnangul ei ole me suutnud ennetustööga viia üldist ühiskondlikku ruumi tasemele, mis muudaks vaba seksuaalkäitumise vähem riskantseks

Maksureformist saab valitsuse kirstunael / Kai Kalamees

Index Scriptorium Estoniae

Kalamees, Kai

2005-01-01

2006. aasta eelarve kokkupanemine ja eelarvestrateegia kinnitamine aastateks 2006-2009 võib aprillis-mais koalitsioonipartnerid taas konfliktini viia, kuna kahe järgneva aasta vältel ei ole võimalik samaaegselt langetada tulumaksu 20 protsendini ja täita koalitsioonileppe lubadusi. Lisad: Reformi juhatuses sisepinged; Maksureform

Omavalitsuste rahastamine vajab muutmist / Olev Raju

Index Scriptorium Estoniae

Raju, Olev, 1948-

2002-01-01

Autor leiab, et omavalitsuste rahastamise reform tuleks Eestis läbi viia Euroopa riikide praktikast ja Eesti praeguse arenguetapi majanduspoliitilise olukorra analüüsist lähtuvalt. Tabel: tulumaksu eraldamise diferentseerimise variante omavalitsuste vahel. Summary: The need for reform in local government funding. Autor: Keskerakond. Parlamendisaadik

Benzin iz rapsa : utopija ili realnaja perspektiva? / Oleg Samorodni

Index Scriptorium Estoniae

Samorodni, Oleg, 1961-

2006-01-01

Suurärimees Rein Kilgi eesmärgiks on viia Lõuna Toiduainetööstus Lõuna-Eesti juhtivaks ettevõtteks, seepärast käib ka võitlus rapsitööstuse Werol Tehased ostmise ümber ärimeeste Oliver Kruuda ja Urmas Sõõrumaaga

The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals.

Science.gov (United States)

Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

2016-06-22

Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs.

Evaluation of the immune response to CRA and FRA recombinant antigens of Trypanosoma cruzi in C57BL/6 mice Avaliação da resposta imune em camundongos C57BL/6 imunizados com os antígenos recombinantes CRA e FRA de Trypanosoma cruzi

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Valéria Rêgo Alves Pereira

2003-07-01

Full Text Available Humoral and cellular immune responses were evaluated in 44 C57BL/6 mice immunized with the Trypanosoma cruzi recombinant antigens CRA and FRA. Both antigens induced cutaneous immediate-type hypersensitivity response. The levels of IgG1, IgG2a, IgG2b and IgG3 were high in CRA immunized mice. IgG3 was the predominant isotype. Although no difference in antibody levels was observed in FRA-immunized mice when compared to control mice, both antigens were able to induce lymphoproliferation in immunized mice. Significant differences were observed between incorporation of [³H]- thymidine by spleen cell stimulated in vitro with CRA or FRA and the control group. These results suggest that CRA and FRA could be involved in mechanisms of resistance to Trypanosoma cruzi infection.As respostas imune humoral e celular foram avaliadas em 44 camundongos C57Bl/6 imunizados com os antígenos recombinantes CRA e FRA de Trypanosoma cruzi. Ambos antígenos induziram reação de hipersensibilidade do tipo imediato. Os níveis de IgG1, IgG2a, IgG2b e IgG3 foram elevados nos camundongos imunizados com CRA. IgG3 foi o isotipo predominante. Nenhuma diferença nos níveis de anticorpos foi observada em camundongos imunizados com FRA em relação aos animais controle. No entanto, ambos antígenos foram capazes de induzir proliferação de linfócitos em camundongos imunizados. Diferenças significativas foram observadas entre a incorporação da timidina - [³H] pelas células esplênicas estimuladas com CRA ou FRA e o grupo controle. Esses resultados sugerem que CRA e FRA poderão estar envolvidos nos mecanismos de resistência à infecção pelo Trypanosoma cruzi.

Rootsi minister : Eesti majanduses esineb ohumärke / Cecilia Malmström ; interv. Raimo Poom

Index Scriptorium Estoniae

Malmström, Cecilia, 1968-

2008-01-01

Rootsi eurominister vastab küsimustele, mis puudutavad Läänemere strateegia kavandamist, Rootsi suhtumist võimalusse viia Läänemere strateegiaga ellu täielik teenuste vaba liikumine siinses regioonis, Eesti majandusolukorra halvenemist, Swedbanki otsust loobuda Hansapanga nimest, Nord Streami gaasijuhet, eesseisvat referendumit Iirimaal Lissaboni lepingu üle

Symposium des Nordost-Instituts zu seutsch-baltischen diplomatischen Beziehungen / Detlef Henning

Index Scriptorium Estoniae

Henning, Detlef, 1959-

2011-01-01

12. oktoobril 2011 toimus Lüneburgis avatud sümpoosion Baltimaade ja Saksamaa vahel diplomaatiliste suhete taastamise kahekümnenda aastapäeva puhul. Ülevaade toimunust. Lüneburgi valikut hinnati igati õnnestunuks ja järgmisel aastal plaanitakse seal läbi viia loengusari Hansalinnade ajaloo teemal

Relvastatud jõu kasutamine / Kalev Stoicescu

Index Scriptorium Estoniae

Stoicescu, Kalev

2006-01-01

Sõjalistes operatsioonides peavad jõu kasutamise reeglid olema piisavalt selged, nende koostamisel arvestatakse oma riigi seadusi ja rahvusvahelist õigust, kuid ka kohalikku kultuuritausta. Liiga kitsad reeglid võivad piirata sõjalise ülema tegevust, liiga laiad või ähmased reeglid aga võivad viia konflikti eskaleerumisele. Näiteid

Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression.

Science.gov (United States)

Roy, Abhishek; Ansari, Shabbir A; Das, Kaushik; Prasad, Ramesh; Bhattacharya, Anindita; Mallik, Suman; Mukherjee, Ashis; Sen, Prosenjit

2017-08-18

Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Blunt trauma with bullet-proof vests. Skin lesions are no reliable predictor of injury severity].

Science.gov (United States)

Doll, D; Illert, B; Bohrer, S; Richter, C; Woelfl, C

2009-04-01

It is well known that so-called bullet-proof vests offer protection against a wide range of penetrating trauma, but their protection against blunt trauma is less well understood. Fast projectiles may result in hematomas and contusions behind the armour. We report a traffic accident involving a young soldier wearing a ballistic protection vest resulting in a right thoracoabdominal blunt trauma leading to a confined liver compression rupture. As nearly no skin marks were detectable, we point out that every emergency department surgeon should be very suspicious if a patient wore a ballistic vest at the time of the accident--there may be no skin marks despite severe intra-abdominal trauma. Our patient recovered following hypotensive ICU treatment, thrombocyte mobilization, and factor VIIa substitution.

Hemostatic resuscitation in postpartum hemorrhage - a supplement to surgery

DEFF Research Database (Denmark)

Ekelund, Kim; Hanke, Gabriele; Stensballe, Jakob

2015-01-01

: This review summarizes the background, current evidence and recommendations with regard to the role of fibrinogen, tranexamic acid, prothrombin complex concentrate, desmopressin, and recombinant factor VIIa in the treatment of patients with postpartum hemorrhage. The benefits and evidence behind traditional...... be considered when hypofibrinogenemia is identified. Early administration of 1-2 g of tranexamic acid is recommended, followed by an additional dose in case of ongoing bleeding. Uncontrolled hemorrhage requires early balanced transfusion. CONCLUSION: Despite the lack of conclusive evidence for optimal...... hemostatic resuscitation in postpartum hemorrhage, the use of viscoelastic hemostatic assays, fibrinogen, tranexamic acid and balanced transfusion therapy may prove to be potentially pivotal in the treatment of postpartum hemorrhage. This article is protected by copyright. All rights reserved....

Trauma and Coagulation

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Murat Yılmaz

2011-08-01

Full Text Available Bleeding and coagulation disorders related to trauma are pathological processes which are frequently seen and increase mortality. For the purpose, trauma patients should be protected from hypoperfusion, hypothermia, acidosis and hemodilution which may aggravate the increase in physiological responses to trauma as anticoagulation and fibrinolysis. Performing damage control surgery and resuscitation and transfusion of adequate blood and blood products in terms of amount and content as stated in protocols may increase the rate of survival. Medical treatments augmenting fibrin formation (fibrinogen, desmopressin, factor VIIa or preventing fibrin degradation (tranexamic acid have been proposed in selected cases but the efficacy of these agents in trauma patients are not proven. (Journal of the Turkish Society Intensive Care 2011; 9:71-6

Recombinant coagulation factor VIIa labelled with the fac-99 mTc(CO)3-core: synthesis and in vitro evaluation of a putative new radiopharmaceutical for imaging in acute bleeding lesion

DEFF Research Database (Denmark)

Madsen, Jacob; Christensen, Jesper B.; Olsen, Ole H.

2011-01-01

Coagulation in blood is initiated when coagulation factor VII (FVII) binds to exposed TF and is activated to FVIIa, and the TF/ FVIIa complex may therefore provide a marker of vascular injury potentially applicable in diagnostic imaging of acute gastrointestinal (GI) bleeding. Methods: Recombinant...... yield and in 495% radiochemical purity. Pull down experiments showed that the biological activity (binding to tissue factor and to anti-FVII antibody) of the radiolabelled product remained intact in the formulation mixture as well as in human serum. By computer modeling analysis, two candidate sites...

Characterization of the Drosophila ortholog of the human Usher Syndrome type 1G protein sans.

Directory of Open Access Journals (Sweden)

Fabio Demontis

Full Text Available BACKGROUND: The Usher syndrome (USH is the most frequent deaf-blindness hereditary disease in humans. Deafness is attributed to the disorganization of stereocilia in the inner ear. USH1, the most severe subtype, is associated with mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15, and sans. Myosin VIIa, harmonin, cadherin 23, and protocadherin 15 physically interact in vitro and localize to stereocilia tips in vivo, indicating that they form functional complexes. Sans, in contrast, localizes to vesicle-like structures beneath the apical membrane of stereocilia-displaying hair cells. How mutations in sans result in deafness and blindness is not well understood. Orthologs of myosin VIIa and protocadherin 15 have been identified in Drosophila melanogaster and their genetic analysis has identified essential roles in auditory perception and microvilli morphogenesis, respectively. PRINCIPAL FINDINGS: Here, we have identified and characterized the Drosophila ortholog of human sans. Drosophila Sans is expressed in tubular organs of the embryo, in lens-secreting cone cells of the adult eye, and in microvilli-displaying follicle cells during oogenesis. Sans mutants are viable, fertile, and mutant follicle cells appear to form microvilli, indicating that Sans is dispensable for fly development and microvilli morphogenesis in the follicle epithelium. In follicle cells, Sans protein localizes, similar to its vertebrate ortholog, to intracellular punctate structures, which we have identified as early endosomes associated with the syntaxin Avalanche. CONCLUSIONS: Our work is consistent with an evolutionary conserved function of Sans in vesicle trafficking. Furthermore it provides a significant basis for further understanding of the role of this Usher syndrome ortholog in development and disease.

Serum zinc and hormonal profile in male dialysis patients receiving human recombinant erythropoietin Zinco sérico e perfil hormonal de pacientes do sexo masculino submetidos à hemodiálise em uso de eritropoetina humana recombinante

Directory of Open Access Journals (Sweden)

Maria Mouranilda Schleicher

2005-08-01

Full Text Available INTRODUCTION: Treatment with recombinant human erythropoietin (rHuEpo is associated with an improvement in well-being and quality of life in patients submitted to maintenance hemodialysis (HD. OBJECTIVES: The goal of this work was to evaluate the levels of sex hormones, hematocrit, albumin and zinc in HD patients with rHuEpo therapy and compare them with those observed in patients without rHuEpo treatment. MATERIAL AND METHODS: Two groups of twelve male HD patients each were selected for a transversal study; one did not receive rHuEpo (group 1 whereas the other one did (group 2. Levels of hematocrit, albumin, zinc, luteinizing hormone (LH, follicle-stimulating hormone (FSH, prolactin, and testosterone were determined. RESULTS: Group 2 patients showed significantly higher medians (p INTRODUÇÃO: Em pacientes submetidos à hemodiálise crônica (HD, o tratamento com eritropoetina humana recombinante (rHuEpo está associado a melhora no bem-estar geral e na qualidade de vida. OBJETIVOS: O objetivo do presente trabalho foi avaliar os níveis dos hormônios sexuais e do zinco em pacientes sob HD e em uso de rHuEpo em comparação com pacientes sem tratamento com essa droga. MATERIAL E MÉTODOS: Dois grupos de doze pacientes do sexo masculino cada um, submetidos à HD, sendo um deles sem uso de rHuEpo (grupo 1 e o outro utilizando a droga (grupo 2, foram selecionados para um estudo transversal, comparando-se os níveis séricos do zinco, da albumina, dos hormônios FSH, LH, prolactina, testosterona e do hematócrito. RESULTADOS: No grupo 2, os valores de testosterona (4,65 vs. 3,5ng/ml, hematócrito (30,5 vs. 22%, albumina (3,9 vs. 3,7g/dl e zinco (62,5 vs. 50,5microg/dl foram significativamente maiores do que no grupo 1 (p < 0,05. DISCUSSÃO: Sugere-se que, em pacientes recipientes da rHuEpo, os níveis mais altos de hematócrito, zinco, albumina e testosterona possam ser fatores que contribuam para melhorar a disfunção sexual e a qualidade de

Hudozhestvennaja akademija pomogajet naiti svojo litso

Index Scriptorium Estoniae

2008-01-01

Eesti Kunstiakadeemia osalemisest innovatsiooniprogrammis Spinno. Projekti eesmärgiks on viia kokku disainiõppureid ja ettevõtteid, suurendada ettevõtjate teadmisi disainist. Spinno raames käivitati Disainiaasta ja Arhitektuuriaasta projektid. Kommenteerib projektijuht Sven Idarand. Tootedisainiga tegelevast Eesti Kunstiakadeemia esimesest spin-off ettevõttest Taikonaut räägib Kristiina Tuubel

Ühendatud Balti Ameerika Komitee eestlaste juhtimisel

Index Scriptorium Estoniae

2005-01-01

alates 2005. aasta märtsist, need on : Mati Kõiva ÜBAK president, Lya Karm - esinaine, Erik Puskar - liige, Karl Altau - büroojuhataja. Peamiseks tegevuseks on USA Kongressi saadikutekojas läbi viia esitatud resolutsioon, mis nõuab, et Venemaa vabandaks 1940. aasta Balti riikide okupeerimise pärast

Eesti ja Venemaa uue külma sõja õhutamise avangardis / Herbert Vainu

Index Scriptorium Estoniae

Vainu, Herbert, 1929-2011

2008-01-01

Eesti ja Venemaa juhtide mängimine rahvustundel tõstab rahvusvahelist pinget, mis võib viia külma sõja taastekkimisele. Autor kritiseerib muuhulgas president Toomas Hendrik Ilvese poliitilist tegevust ja esinemist Hantõ-Manskiiskis toimunud soome-ugri maailmakongressil. Vabariigi President töövisiidil Venemaal 27.-30.06.2008

Ajateenistusest, ausalt! / Kim Järvepõld

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Järvepõld, Kim

2007-01-01

Ilmunud ka: Postimees : na russkom jazõke, 9. apr. 2007, lk. 7. Autor leiab, et põhiseaduslik nõue, mille järgi on kõik Eesti kodanikud kohustatud osa võtma riigikaitsest, pole vastavuses tegeliku olukorraga, ning arvab, et kohustuslik ajateenistus tuleb kaotada või viia kooskõlla põhiseadusega

Latvijas Gaze buyback likely to flop

Index Scriptorium Estoniae

2003-01-01

Veerandi Läti gaasifirma Latvijas Gaze omanik Itera kavatseb lähiajal lõpule viia üheksa protsendi Läti firma aktsiate müügi ettevõttele Gazprom. Gazprom'i kontrolli all on praegu 25 protsenti, Ruhrgas'il 28,66 ning E.ON Energie AG-l 18,06 protsenti Latvijas Gaze aktsiatest

75 FR 76930 - Amendment to the International Traffic in Arms Regulations: Revision of U.S. Munitions List...

Science.gov (United States)

2010-12-10

... specially designed for producing, processing, or using: (i) WMDs; (ii) Special nuclear materials; or (iii...)(2)(iii): VII(a)(2)(iii) also includes B kits (add-on armor). (iv) (Tier 3) Deep water fording kits... instructions written or recorded on other media or devices such as disk, tape, read-only memories. Dated...

Lääne- ja Ida-Virumaal satub löögi alla tuhatkond töökohta / Raivo Raigna

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Raigna, Raivo

2009-01-01

Puidu põletamine elektrijaamades on tõstnud ümarpuidu hinda Virumaal kuni 40%, selline kunstlik ja järsk toorme hinnatõus hävitab kahe Virumaa suurtööandja, puitlaastplaatide tootja Repo Vabrikud ja puitmassitehase Estonian Cell konkurentsivõime rahvusvahelistel turgudel ning võib viia sadade töökohtade kaotuseni

Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

Science.gov (United States)

Arumugam, Jayavel; Bukkapatnam, Satish T S; Narayanan, Krishna R; Srinivasa, Arun R

2016-01-01

Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin) using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve). In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features) using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

Directory of Open Access Journals (Sweden)

Jayavel Arumugam

Full Text Available Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve. In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

Evaluaci??n de la biosimilitud y comparabilidad de medicamentos biosimilares

OpenAIRE

Calvo Hern??ez, Bego??a; Z????iga Hernando, Leyre; G??mez L??pez-Tello, Paloma

2013-01-01

Al finalizar el periodo de patente de los medicamentos de origen biotecnol??gico, como las prote??nas de origen recombinante y los anticuerpos monoclonales, se ha abierto la posibilidad de fabricar copias de dichos f??rmacos, denominados medicamentos biosimilares. Para conseguir la aprobaci??n de estos f??rmacos no es aplicable el marco legal existente para los gen??ricos, ya que los biosimilares son productos similares pero no id??nticos al medicamento innovador. El fabricante del medicam...

Diagnóstico molecular para Leishmaniasis

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Ysabel Montoya

1997-01-01

Full Text Available El potencial diagnóstico de epitopes inmunodominantes seleccionados fue ensayado satisfactoriamente a fin de obtener una prueba serodiagnóstica alternativa para la Leishmaniasis Tegumentaria Americana. Dos proteínas recombinantes prometedoras de L. (v. peruviana referidas como T-26-U2/T26-U4 fueron reconocidas por sueros individuales de pacientes con Leishmaniasis Tegumentaria Americana usando Western Blot. La sensibilidad de la prueba fue de 86% con sueros permanentes con Leishmaniasis peruana.

EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat.

Directory of Open Access Journals (Sweden)

Marisa Zallocchi

Full Text Available Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific, EIAV-CMV-MYO7A (UshStat or EIAV-CMV-Null (control vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.

EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat.

Science.gov (United States)

Zallocchi, Marisa; Binley, Katie; Lad, Yatish; Ellis, Scott; Widdowson, Peter; Iqball, Sharifah; Scripps, Vicky; Kelleher, Michelle; Loader, Julie; Miskin, James; Peng, You-Wei; Wang, Wei-Min; Cheung, Linda; Delimont, Duane; Mitrophanous, Kyriacos A; Cosgrove, Dominic

2014-01-01

Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.

St. Ola sõitis Virumaa lipulaevana Soome / Gerli Romanovitsh

Index Scriptorium Estoniae

Romanovitš, Gerli, 1977-

2005-01-01

Ilmunud ka: Severnoje Poberezhje 10. juuni lk 1,4. Parvlaev St. Ola alustas sõitu Sillamäelt Kotkasse, et viia Ida-Virumaa esindajad Kouvolas toimuvale messile, millest poole võtab enda alla Virumaa väljapanek. Järgmisel aastal käivitub Sillamäe-Kotka regulaarlaevaliin. Ida-Viru maavanema Ago Silde kommentaar

XXI sajandil võib vabalt puhkeda demokraatia kriis / Jaan Kaplinski

Index Scriptorium Estoniae

Kaplinski, Jaan, 1941-

2007-01-01

Ilmunud ka: Delovõje Vedomosti 4. apr. lk. 12. Autor usub, et XXI sajand saab otsustavaks ajaks nii inimsoo kui ka demokraatia jätkusuutlikkusele. Pole võimatu, et elatustaseme langus ja suure osa inimeste võimetus sellega leppida ning leida võimalus ka kasinates tingimustes hästi elada võib viia demokraatia kriisile

Mazheikiu tehast varustav Vene naftajuhe kuival / Martti Kass

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Kass, Martti

2006-01-01

Delfi.lv andmetel pole juba kaheksa päeva Mazheikiai naftatehas Venemaalt naftat saanud. Lätis prognoositakse bensiinihinna olulist tõusu. USA suursaadik Leedus Keith Smith on hoiatanud, et Mazheikiai naftatehasel võib uue omaniku käe all tarneprobleeme tekkida, tema väitel on tunda survet, et Mazheikiai naftatehas taas Venemaa omandusse viia

Institute for Plasma Research, Stuttgart University. Annual report 1986

International Nuclear Information System (INIS)

1987-01-01

In 1986 the IPP-IPF cooperation in the field of fusion related research and development has been successfully continued. The ECRH project as the largest activity is concentrated on the completion of the 1 MW/70 GHz long-pulse ECRH-system for the W VII-AS stellarator. The components tests promise optimum technical and - hopefully - physical results. Theoretical investigations mainly concern ray propagation and time dependent transport calculations for stellarators at ECRH conditions. A first successful experimental demonstration of the LIDAR scattering concept on JET was a rather encouraging progress for the laser diagnostic group. Besides this project the FIR scattering was continued on ASDEX with measurements of the k-spectra of the low frequency fluctuations during the various kinds of plasma heating. On the WEGA stellarator a programme of flux surface measurements with electron beams has been started. A meanwhile improved detection method will be applied - in cooperation with the Wendelstein team - at the coming W VII-AS stellarator. In the last year the plasma focus experiment POSEIDON achieved successful operation at full bank energy. (orig.)

Perspectives on confinement in helical systems

International Nuclear Information System (INIS)

Itoh, Kimitaka; Itoh, Sanae

1989-01-01

A review on recent experimental results and theoretical models on anomalous transport and density limit in toroidal helical devices is presented. Importance of transport problems is discussed. Experiments on Heliotron-E, Wendelstein-VIIA and new devices, i.e., ATF, Wendelstein-VIIAS and CHS, are reviewed and an overview on confinement property is given. From recent experimental results one sees that there are anomalous transport, which increases with temperature, and density limit, and that they limit the energy confinement time as well as the attainable beta value. The confinement characteristics of the scrape off layer plasma and loss cone loss are discussed, and perspectives on the high temperature plasma are given. These anomalous transport and density limit will be difficult obstacles in realizing a reactor grade plasma in helical systems. It is an urgent task to draw a realistic picture of the confinement based on the present data base. The relevant knowledge now would be critically essential for the successful development of the research in 1990's. (author) 102 refs

A Novel Homozygous MYO7A Mutation: Case Report

Directory of Open Access Journals (Sweden)

Mahsa Ahmadi

2018-05-01

Full Text Available MYO7A is an unconventional myosin that is essential for ordinary hearing and vision; mutations in the MYO7A gene result in Usher syndrome type 1B and other disorders. In this manuscript, we reported a mutation (c.4705delA in exon 35, causing the alteration of a Ser amino acid to Ala at codon 1569 (p.H2027del located within the first FERMdomain of the human protein myosin VIIA. This mutation involved in the pathogenesis of hearing loss, congenital night blindness, muscular weakness, skin problem, and difficulty in keeping balance in the 13-year-old female. After checkup the patient’s DNA was extracted from peripheral blood and amplification was performed by PCR. Sequencing method was performed for identification of the mutation. The c.4705delA mutation in exon 35 was found in the patient in heterozygosis form; this means that her mother and father were carriers. This mutation is located on the tail of the myosinVIIA protein and is associated with several disorders.

The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

Science.gov (United States)

Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

2016-01-01

Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs. DOI: http://dx.doi.org/10.7554/eLife.15258.001 PMID:27331610

Effects of sucrose on rFVIIa aggregation and methionine oxidation

DEFF Research Database (Denmark)

Soenderkaer, Susanne; Carpenter, John F; van de Weert, Marco

2004-01-01

The aim of this study was to characterize the effects of sucrose on the stability of recombinant factor VIIa (rFVIIa), with special emphasis on aggregation and methionine oxidation, as well as to investigate the impact of various environmental conditions on the rFVIIa conformation. The stability...... of rFVIIa was studied at pH 5. Aggregation was monitored using size exclusion high-performance liquid chromatography (SE-HPLC), whereas formation of methionine oxidation products was measured by reversed-phase high-performance liquid chromatography (RP-HPLC). Fourier transform infrared (FTIR...... the protein's surface, which shifts the protein molecular population away from expanded aggregation competent species and toward the compact native state, is thought to account for these observations. rFVIIa is sensitive to methionine oxidation; two mono-oxidized and one di-oxidized product were formed upon...

Riigikogu liige ei vaja hooldusassistenti / Ignar Fjuk

Index Scriptorium Estoniae

Fjuk, Ignar, 1953-

2001-01-01

Ilmunud ka: Järva Teataja, 11. sept. 2001, lk. 2; Nädaline, 11. sept. 2001, lk. 4; Vooremaa, 11. sept. 2001, lk. 2; Võrumaa Teataja, 11. sept. 2001, lk. 2; Valgamaalane, 22. sept. 2001, lk. 2. Noorpoliitikud Keskerakonnast pöördusid Riigikogu poole ettepanekuga viia Eesti parlamendis sisse assitendi süsteem. Autor: Reformierakond. Parlamendisaadik

Kubilius conquers America / Rokas M. Tracevskis

Index Scriptorium Estoniae

Tracevskis, Rokas M.

2010-01-01

5.- 9. maini kestnud Ameerika Ühendriikide visiidi ajal kohtus Leedu peaminister Andrius Kubilius riigisekretäri Hillary Rodham Clintoniga, kellega räägiti riikidevahelistest suhetest, CIA salavanglast ja Egle Kusaitest, kes väidetavalt plaanis Venemaa sõjalistel objektidel läbi viia terrorirünnakud. Andrius Kubilius kohtus ka IBMi esindajatega. IBM plaanib rajada Leetu uurimiskeskuse

Peetri maja kant Kadriorus saab peagi uue näo / Ulvar Käärt

Index Scriptorium Estoniae

Käärt, Ulvar, 1982-

2009-01-01

Kadrioru pargis asuva Peeter I maja ja presidendi kantselei vahelise pargiala uuendustöödest. Vt. samas: Presidendi lossi esine suletakse. Peetri aia rekonstrueerimistööde käigus on plaanis pargi territooriumile üle viia ka praegu presidendi kantselei esist paraadplatsi läbiv kõnnitee, kuna kantseleil on plaanis hoone esine ümbritseda piirdeaiaga

IMF soovitab uue töölepinguseaduse kiiresti vastu võtta / Peep Lillemägi

Index Scriptorium Estoniae

Lillemägi, Peep, 1967-

2008-01-01

Ilmunud ka: Tallinnskii Vestnik juuli 2008, lk. 3. Eestis viibinud IMF-i delegatsiooni hinnangul sõltub Eesti majanduskasvu taastumine suurel määral majanduse konkurentsivõimest, delegatsioon toetab kavatsust leida edasisi võimalusi kokkuhoiuks ning soovitab töölepinguseaduse eelnõu kiiresti vastu võtta ja ellu viia. Rahandusminister Ivari Padari arvamus IMF-i hinnangute kohta

Veel kord riigi poolsest teoprovokatsioonist : kas keelatud või siiski lubatud? / Paavo Randma

Index Scriptorium Estoniae

Randma, Paavo, 1977-

2006-01-01

Agent provocateur'i mõistest ja lubatavusest Inglismaa, Saksamaa ja Portugali kohtupraktika näitel. Agent provocateur on isik, kes politseiametniku või eraisikuna kriminaalmenetlust toimetavate asutuste ülesandel või heakskiidul kihutab teise isiku kuritegu toime panema eesmärgiga ta kinni võtta ja tema suhtes läbi viia kriminaalmenetlus, mis päädiks karistusega

Nam ljubõje dorogi dorogi / Sergei Kolikov

Index Scriptorium Estoniae

Kolikov, Sergei

2004-01-01

Tänavu on remonditakse Tallinn-Tartu maanteed 183 miljoni krooni eest, 60 kilomeetrise Tallinn-Peterburi maanteelõigu rekonstrueerimiseks määras Euroopa Komisjon küll 392 miljonit krooni, kuid töö lükkub järgmisse aastasse. Teetööde vähenemine võib mõned ettevõtted viia pankroti piirile

[Syndromic hereditary deafness. Usher's syndrome. Oto-neurologic and genetic factors].

Science.gov (United States)

Espinós, C; Pérez-Garrigues, H; Beneyto, M; Vilela, C; Rodrigo, O; Nájera, C

1999-01-01

Usher syndrome (USH) is an autosomal recessive hereditary disorder characterized by congenital bilateral sensorineural hearing loss and progressive loss of vision due to retinitis pigmentosa (RP). The prevalence of Usher syndrome is estimated to be 3-4.4 cases per 100.000 people. Several clinical types have been distinguished by age at onset, rate of progression, and severity of symptoms. Type I (USH1) is characterized by a congenital, severe-to-profound deafness and absent vestibular function. Type II (USH2) shows a congenital and moderate-to-severe hearing loss and normal vestibular response. It is also suggested a third type (USH3), clinically similar to USH2, but with progressive hearing loss. Genetic heterogeneity of USH is quite extensive. Up to now, seven different loci responsible for the defect are known: 14q, 11q, 11p, 10q and 21q for USH1; 1q for USH2 and 3q for USH3. Moreover, there are USH1 and USH2 families that fail to show linkage to these candidate regions demonstrating that should exist other loci causing USH, although their ubications are unknown. To date, only two genes involved in the USH pathology are known, although together they are responsibles of about the 80% of total USH cases: myosin VIIA, an unconventional myosin, involved in the USH1b phenotype and a protein similar to the laminina, responsible for the USH2a phenotype.

Prevalencia de anticuerpos contra Trypanosoma cruzi en donadores de sangre del IMSS, Orizaba, Veracruz, México

OpenAIRE

Ramos-Ligonio Angel; Ramírez-Sánchez Michaía Elián; González-Hernández Juan Carlos; Rosales-Encina José Luis; López-Monteon Aracely

2006-01-01

OBJETIVO: Determinar la prevalencia de anticuerpos contra Trypanosoma cruzi en donadores del Hospital General Regional del Instituto Mexicano del Seguro Social (IMSS) en la ciudad de Orizaba, Veracruz. MATERIAL Y MÉTODOS: Se examinaron muestras de donadores del banco de sangre del Hospital General Regional (HGRO) del IMSS para la búsqueda de antiT. cruzi por ELISA, Western blot e IFI, utilizando una proteína recombinante (MBP::Hsp70) y un extracto crudo de epimastigotes. Las muestras fueron o...

Desarrollo de vacunas contra el virus de la inmunodeficiencia humana tipo 1: Relevancia de la inmunidad celular contra subtipos Development of vaccines for HIV-1: Relevance of subtype-specific cellular immunity

Directory of Open Access Journals (Sweden)

Ana María Rodríguez

2010-12-01

Full Text Available Han pasado casi 30 años de la detección de los primeros casos de infección con HIV-1 y aún no se ha conseguido desarrollar una vacuna efectiva y segura. A pesar del impacto positivo sobre la pandemia que se ha conseguido gracias a los avances en la terapia antirretroviral (TARV, el HIV/sida sigue constituyendo un grave problema para la salud pública, especialmente en los países en desarrollo, donde es difícil el acceso al tratamiento. En el mundo, 33 millones de personas viven con el virus del sida, mientras que en la Argentina se calcula que habría unos 120 000 infectados. Uno de los desafíos para lograr una vacuna contra el HIV es la variabilidad viral. El grupo M, responsable de la pandemia, se encuentra dividido en 10 subtipos y varios sub-subtipos, además de las 48 formas recombinantes circulantes y más de cien formas recombinantes únicas. La epidemia de HIV en nuestro país es tan compleja como en el resto del mundo, con la co-circulación principalmente de virus pertenecientes al subtipo B y recombinantes BF (CRF12_BF y derivadas. A pesar de la cantidad de trabajos dedicados a la caracterización de la respuesta inmune y al desarrollo de vacunas, no queda claro cuál es el impacto de la variabilidad en la elección del antígeno. Trabajos realizados en nuestro laboratorio demuestran el papel que juega la inmunidad celular con respecto a las variantes recombinantes BF, tanto en humanos como en modelos animales. Estos resultados son de importancia en el desarrollo de futuras vacunas para nuestra región.It has been almost 30 years since the detection of the first HIV-1 cases and yet an effective and safe vaccine has not been developed. Although, advances in antiretroviral therapy (HAART have produced a major impact on the pandemic, and even though HIV/aids remains a major concern for developing countries, where access to therapy is limited. The last report from UNAIDS notified 33 million people living with HIV/aids, worldwide

Leptospirose animal: estudos para o desenvolvimento de vacinas recombinantes

OpenAIRE

Felix, Samuel Rodrigues

2013-01-01

A leptospirose é uma doença causada por espiroquetas do gênero Leptospira. É uma zoonose de ampla distribuição geográfica, sendo um problema de saúde pública e veterinária, principalmente em países subdesenvolvidos e em desenvolvimento de clima tropical e subtropical. Em medicina veterinária, a leptospirose é uma doença importante tanto para a clínica quanto para a produção, devido ao risco à saúde pública, perdas reprodutivas e óbitos. A vacinação animal é realizada como medida de prevenção ...

Metoodika lapse emotsionaalse väärkohtlemise hindamiseks institutsionaalses keskkonnas / Triin Edovald

Index Scriptorium Estoniae

Edovald, Triin

2001-01-01

Uurimusest, mille eesmärgiks oli lapse emotsionaalse väärkohtlemise hindamise metoodika kohandamine lastekodu tingimustele. Uurimus viidi läbi ühes Tartu lastekodus, intervjueerides kuut kasvatajat ja vaadeldes kuue lastekodulapse ja tema usalduskasvataja vahelist suhtlemist ja tegevust eesmärgiga sisse viia võimalikud täpsustused ja muutused emotsionaalse väärkohtlemise hindamise metoodikasse kohandades seda lastekodu tingimustele

Mõeldes arhitektuuri välkloengutele = Considering flash lectures on architecture / Margit Mutso

Index Scriptorium Estoniae

Mutso, Margit, 1966-

2010-01-01

7. veebruaril 2008 Von Krahli Teatris alanud arhitektuuri välkloengutest, mille eesmärk oli haarata avalikkust kaasa mõtlema, rääkima meid ümbritsevast keskkonnast ning viia ühiskonda arusaamist, et arhitektuur on meie kõigi asi. Arhitektuurist kutsuti rääkima tuntud äri- ja kultuuriinimesi. Välkloenguid modereerisid Ülar Mark, Margit Mutso ja Mattias Agabus

Euroopa firmad on asunud oma äri ümber korraldama / Ralph Atkins, Peggy Hollinger

Index Scriptorium Estoniae

Atkins, Ralph

2004-01-01

Euroopa Liidu juhtide sõnul liigutakse aeglaselt 2000. aastal Lissaboni tippkohtumisel seatud sihtidele viia Euroopa majandus konkurentsivõimelt esikohale maailmas. Euroopa ettevõtted on asunud äri ümberstruktureerima eesmärgiga kärpida kulusid ja leida firmade konkurentsieeliseid. Lisad: Muundumine nagu õpikus; Ümberkorraldamise tulemused siiani teadmata; Erik Aru. Eestis on eduka restruktureerimise näiteks Baltika ja Harju Elekter

Rohkem kui 300 aastat tagasi surnud pere õnnestus tuvastada / Mati Mandel ; Kalev Jaago

Index Scriptorium Estoniae

Mandel, Mati, 1945-

2016-01-01

Peanse külas Lihula vallas toimunud kaevamistest. Leiti nelja inimese luustikud. Leiumaterjal võimaldas võrrelda ja kokku viia arheoloogi, numismaatiku, atropoloogi ja arhivaari uurimistulemusi. Suure tõenäosusega võisid leitud maetud olla Leti Andrese Mihkel, tema abikaasa ning lapsed Heinrich ja Ann. Tegu võib olla 1710.- 1711. aasta katku ohvritega. Haruldase juhtumina saab luid seostada konkreetsete ajalooliste isikutega

Euroopa Liit valmistab ette uutmoodi Venemaa-poliitikat / Ahto Lobjakas

Index Scriptorium Estoniae

Lobjakas, Ahto, 1970-

2006-01-01

EL-i järgmine eesistujariik Saksamaa pakub täielikku paradigma muutust EL-i ja Venemaa suhetes, autori sõnul asenduks senine rõhk "ühistel väärtustel" huvide kaine kalkulatsiooniga. Autor esitab oma seisukoha, kuidas peaks toimima Eesti: probleemid Venemaaga on vaja viia miinimumini ning EL-is tuleb toetada ühiseid valikuid vetoõiguse ja erahuvide vastu

Kuidas valiti president 1996. aastal? / Rein Toomla

Index Scriptorium Estoniae

Toomla, Rein, 1951-

2002-01-01

Autor leiab 1996. aasta presidendivalimisi analüüsides, et oluliseks tuleb pidada seda, et valimised suudeti põhiseaduses ettenähtud korras läbi viia ning ei pidanud käivituma erakorraliste valimiste mehhanism. Tabelid: 1995. a. Riigikogu valimised; Riigikogu fraktsioonid 1996. a. suvel; Toetus presidendikandidaatidele; Presidendivalimised Riigikogus; Arvatavasti Lennart Meri poolt; Arvatavasti Arnold Rüütli poolt; Presidendivalimised Valimiskogus

Euroopa hing / Joseph Ratzinger ; tõlk. Külli-Riin Tigasson

Index Scriptorium Estoniae

Ratzinger, Joseph

2005-01-01

Paavst Benedictus XVI sõnul võib moraalsete väärtuste purunemine viia Euroopa identiteedi enesehävitamiseni. Inimväärikusest ja inimõigustest peab kujunema tingimusteta väärtus, ka on Euroopa identiteedi jaoks keskne tähtsus abielul ja perekonnal. Sõnavabadusel peab olema piir: teise inimese au ega väärikust ei tohi haavata

Severe hyponatraemia after terlipressin treatment in the patient with surgically untreatable bleeding into gastrointestinal system

International Nuclear Information System (INIS)

Vojtko, M.; Smolar, M.; Laca, L.; Danova, I.; Strelka, L.; Hulo, E.; Mikolajcik, A.; Kicina, R.; Laca, L.; Zelenak, K.

2014-01-01

The authors present the case report of a 46 year old woman. In personal history, she was operated for congenital duodenal stenosis at the age 2 days, later reoperated due to restenosis. The patient had congenital vascular malformations of gastrointestinal tract (GIT) and was recurrently hospitalized for recidivous bleeding into GIT with concurrent development of portal hypertension. In 2012 she was admitted to our department because of relapsing bleeding into GIT which was impossible surgically treated so the patient was treated conservatively. In the course of terlipressin use, sharp decline of natremia developed with subsequent altered consciousness with CT verified brain edema. Further management included discontinuation of terlipressin, slow correction of hyponatraemia, embolization of arterial lienalis, hemosubstitution and recombinant factor VIIa. This treatment led to stop bleeding and improvement of state of consciousness however mild form of organic psycho syndrome persists. (author)

Dengue, zika, chikungunya y el desarrollo de vacunas

OpenAIRE

Kantor, Isabel N

2018-01-01

Dengue (DENV), zika (ZIKV) y chikungunya (CHIKV), tres arbovirosis transmitidas por mosquitos Aedes, se han propagado en las últimas décadas en zonas tropicales y subtropicales húmedas. El dengue es epidémico en áreas subtropicales de la Argentina. Después de la infección por DENV hay inmunidad duradera contra el serotipo infectante, pero aumenta el riesgo de enfermedad grave por los otros tres. La vacuna recombinante tetravalente, Dengvaxia® previene el dengue grave y la hospitalización en s...

Superparamagnetic nanoparticles for cell tracking and magnetic vectorization in ischemic stroke

OpenAIRE

Argibay González, Bárbara

2015-01-01

Las enfermedades cerebrovasculares son la segunda causa de muerte y la primera de discapacidad en países desarrollados. Sin embargo, las terapias disponibles son limitadas. La trombolisis farmacológica o la reperfusión mecánica son las estrategias que reportan mejores beneficios a los pacientes, en términos de pronóstico neurológico, siendo el activador tisular del plasminógeno recombinante (rt-PA) el más común de todos ellos. Recientemente, la terapia celular ha surgido com...

Guía clínica de la enfermedad de Pompe de inicio tardío

OpenAIRE

Barba-Romero, Miguel A.; Barrot, Emilia; Bautista-Lorite, Juan; Gutiérrez-Rivas, Eduardo; Illa, Isabel; Jiménez, Luis M.; Ley-Martos, Myriam; López de Munain, Adolfo; Pardo, Julio; Pascual-Pascual, Samuel I.; Pérez-López, Jordi; Solera, Jesús; Vílchez-Padilla, Juan J.

2012-01-01

English version available at www.neurologia.com Hasta 2006, la enfermedad de Pompe o glucogenosis tipo II era una enfermedad incurable y con tratamiento meramente paliativo. El desarrollo de la terapia de sustitución con la enzima α-glucosidasa recombinante humana ha constituido el primer tratamiento específico para esta enfermedad. El objetivo de esta guía es servir de referencia en el manejo de la variedad de inicio tardío de la enfermedad de Pompe, es decir, la que aparece d...

Oral vaccines against diarrhea associated with enteropathogenic Escherichia coli strains based on genetically modified Bacillus subtilis strains

OpenAIRE

Wilson Barros Luiz

2010-01-01

O objetivo deste trabalho foi a construção de linhagens geneticamente modificadas de B. subtilis capazes de expressar porções de intimina, principal componente envolvido na capacidade de colonização de linhagens enteropatogênicas de Escherichia coli (EPEC), como estratégia vacinal de administração oral contra diarréias infecciosas. As vacinas desenvolvidas empregaram cinco regiões da intimina de EPEC e linhagens de B. subtilis capazes de expressar e acumular proteínas recombinantes no citopla...

The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease

Directory of Open Access Journals (Sweden)

Michael Schuliga

2015-01-01

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

Status of stellarator research

International Nuclear Information System (INIS)

Wobig, H.

1985-01-01

In recent years main activities in stellarator research were focussed on production and investigation of currentless plasmas. Several heating methods have been applied: electron cyclotron heating, ion cyclotron heating and neutral beam injection. The parameters achieved in HELIOTRON E and W VII-A are: antin 20 m 3 , Tsub(i) <= 1 keV. The confinement is improved as compared with ohmically heated discharges. By ECRH (P = 200 kW) it is possible to heat electrons up to 1.4 keV, confinement in this regime is dominated already by trapped particle effects. Toroidal currents up to 2 kA - either bootstrap currents or externally driven currents - were observed. High β-values (antiβ = 2%) have been obtained in HELIOTRON E, in this regime already pressure driven MHD-modes were observed. Future experiments (ATF-1 and W VII-AS) will extend the parameter regime to temperatures of several keV. These experiments will give important information about critical problems of the stellarator line (β-limit, neoclassical confinement impurity transport). A few reactor studies of stellarators exist, attention is mainly concentrated on technical problems of the modular coil system

Desarrollo de una vacuna profiláctica de segunda generación contra el papilomavirus humano

Directory of Open Access Journals (Sweden)

Alonso Leonardo

2011-06-01

Full Text Available Los papilomavirus humanos (HPV son el agente etiológico del cáncer cervical (CC, la segunda causa de muerte por cáncer en mujeres. Se estima que medio millón de nuevos cánceres se diagnostica cada año, ocurriendo la mayoría de ellos en países en vías de desarrollo debido a la ausencia o ineficiencia de los programas masivos de detección temprana. Recientemente se han introducido en el mercado dos vacunas profilácticas contra las principales cepas oncogénicas de HPV, la cepa 16 y 18, responsables por el 80% de todos los CC. Estas vacunas se obtienen en forma recombinante y han demostrado ser extremadamente seguras y eficaces. Sin embargo, su impacto inmediato en la incidencia de la infección por HPV en países en vías de desarrollo será mínimo, debido principalmente al alto costo de las mismas. Existe la necesidad de contar con vacunas de segunda generación, de bajo costo y de aplicación masiva que permitan disminuir sensiblemente el número de CC en la población. Con este objetivo hemos desarrollado una plataforma de expresión recombinante que permite obtener partículas tipo virus (VLPs con las cuales es posible formular vacunas efectivas y accesibles contra la infección por HPV.

Kodanikud, võltsingud ja zombid / Tanel Tammet

Index Scriptorium Estoniae

Tammet, Tanel

2005-01-01

Autor avaldab arvamust, et e-valimiste vastu olevad erakonnad ja poliitikud pole mures mitte niivõrd nende valimiste turvalisuse pärast, vaid pigem seepärast, et e-valimised võivad suurendada noorema valijaskonna aktiivsust. E-valimiste õnnestumine võib viia mõttele Šveitsi otsedemokraatia mõne põhimõtte rakendamise kohta Eestis. Autor kirjeldab turvariske, mis võivad kaasneda e-valimistel

Valitsuse stabiilsus Eestis : soovunelm või tegelikkus? / Olaf Dahlmann

Index Scriptorium Estoniae

Dahlmann, Olaf

2003-01-01

Autor leiab, et hoolimata sagedastest valitsuste vahetumistest, pingetest sisepoliitikas ja rahva üha süvenevast poliitilisest apaatsusest, on Eesti suutnud edukalt läbi viia poliitilisi reforme. Üldine konsensus põhilistes küsimustes on peamiste poliitiliste eesmärkide ja reformipoliitika püsivuse alus, seega ka ka valitsuse stabiilsuse alus. Tabel: Eesti valitsused alates 1992. aastast. Joonis: Valitsuse stabiilsust mõjutavad tegurid

Me ei tohi peatuda / Harri Õunapuu

Index Scriptorium Estoniae

Õunapuu, Harri, 1947-

2006-01-01

Ilmunud ka: Põhjarannik, Severnoje Poberezhje 3. mai lk. 2, Nädaline, Võrumaa Teataja, Vooremaa 4. mai lk. 3,2,2, Harjumaa 5. mai lk. 2, Meie Maa 6. mai lk. 2, Hiiu Leht 9. mai lk. 2, Valgamaalane 16. mai lk. 2, Sakala 24. mai lk. 2. Autori sõnul on Reformierakonna poolt seatud eesmärk viia Eesti viie jõukama riigi sekka Euroopas saavutatav

Eesti gaasiküsimustes : õnnis nagu palderjani nuusutanud kass / Virkko Lepassalu

Index Scriptorium Estoniae

Lepassalu, Virkko, 1971-

2008-01-01

Kehtiva Euroopa Liidu nn gaasidirektiivi 55/2003 järgi soovitatakse gaasi tootmine ja levitamine viia eraldi ettevõtete kätte, praegu ettevalmistatav regulatsioon muudaks selle kohustuslikuks. Seega peaks Gazprom oma 37% -lise osaluse Eesti Gaasis maha müüma. Eesti Gaasi kui sisulise monopolisti hoidmine Gazpromi filiaalina Eestis ohustab otseselt meie julgeolekut. Vt. samas: Välisminister Urmas Paeti kiri Nord Streamile; Nord Streami kaanepoisid

Nähtamatu naise nähtav panus / Eerik Purje ; fotod: V. Sarapuu

Index Scriptorium Estoniae

Purje, Eerik, 1927-

2006-01-01

17. oktoobri õhtul Tartu College´i saalis toimunud pidulikust õhtust, mis oli pühendatud Vaiki Toile, esitades Roman Toi loomingut ja tähistades Romani 90. sünnipäeva. Õhtut juhtis Avo Kittask, esinesid Estonia Koor, Toronto Eesti Meeskoor, lauluansambel Helin, klaveril saatis Asta Ballstadt, koore juhatasid Margit Viia-Maiste, Ingrid Silm, Charles Kipper. Avati kunstnik Josef Milczarski portree juubilarist

Hematoma Expansion Following Acute Intracerebral Hemorrhage

Science.gov (United States)

Brouwers, H. Bart; Greenberg, Steven M.

2013-01-01

Intracerebral hemorrhage, the most devastating form of stroke, has no specific therapy proven to improve outcome by randomized controlled trial. Location and baseline hematoma volume are strong predictors of mortality, but are non-modifiable by the time of diagnosis. Expansion of the initial hematoma is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for hematoma expansion have been identified, including baseline ICH volume, early presentation after symptom onset, anticoagulation, and the CT angiography spot sign. Although the biological mechanisms of hematoma expansion remain unclear, accumulating evidence supports a model of ongoing secondary bleeding from ruptured adjacent vessels surrounding the initial bleeding site. Several large clinical trials testing therapies aimed at preventing hematoma expansion are in progress, including aggressive blood pressure reduction, treatment with recombinant factor VIIa guided by CT angiography findings, and surgical intervention for superficial hematomas without intraventricular extension. Hematoma expansion is so far the only marker of outcome that is amenable to treatment and thus a potentially important therapeutic target. PMID:23466430

Detection and quantification of genetically modified organisms in food and food ingredients

OpenAIRE

Conceição, Fabricio Rochedo; Moreira, Ângela Nunes; Binsfeld, Pedro Canisio

2006-01-01

O cumprimento da legislação que regulamenta a comercialização de alimentos e ingredientes contendo Organismos Geneticamente Modificados (OGMs) é totalmente dependente da sensibilidade e confiabilidade dos métodos de detecção e quantificação de OGMs. Na presente revisão, foram discutidos os métodos mais relevantes para tais fins, especialmente aqueles que se baseiam na detecção da proteína ou do DNA recombinante, destacando as suas principais propriedades, limitações e vantagens. A regulamenta...

Options to the bioindustry in Latin America

OpenAIRE

R. Quintero

1998-01-01

La biotecnología moderna se inició en 1976 con la fundación de la empresa Genentech en Estados Unidos, a partir de esa fecha, se establecieron nuevas empresas que usan cotidianamente en sus sistemas de producción a organismos transformados genéticamente (recombinantes) en diversos sectores de economía, también se amplió el espectro de los organismos vivos productores, utilizando bacterias, levaduras, hongos, células animales y células vegetales (Glick, 1998). Esta nueva tecnología generó enor...

Estudio de la producción heteróloga de una lipasa del hongo Rhizopus oryzae en la levadura metilotrófica Pichia pastoris

OpenAIRE

Serrano González, Alicia

2004-01-01

Consultable des del TDX Títol obtingut de la portada digitalitzada El trabajo recoge los principales aspectos de la producción recombinante de una lipasa del hongo Rhizopus oryzae (ROL) expresada en la levadura Pichia pastoris. El sistema de expresión empleado está basado en la utilización del promotor de la alcohol oxidasa (PAOX1) de la levadura y, por lo tanto es dependiente de la utilización de metanol como substrato inductor. El trabajo recoge una serie de estudios de producción en ...

La trombectomía mecánica en el tratamiento de accidentes cerebrovasculares (ACV) en la fase aguda

OpenAIRE

Alain Bonafe

2013-01-01

En Francia, la incidencia anual de accidentes cerebro vasculares (ACV) es de 1.6 a 2.4 por cada mil (1.000) personas, es decir entre 100.000 y 145.000 por año, con una mortalidad del 15 al 20% al cabo del primer mes y un 75% de personas sobrevivientes con secuelas. El tratamiento de preferencia es la Trombólisis IV (Intra Venosa) con rt-PA (Recombinant Tissue Plasminogen Activator - Activador del Plasminógeno Tisular Recombinante), el cual tiene una ventana de eficacia...

Aplicaciones de la biología molecular en el aparato locomotor (proteína morfogenética ósea)

OpenAIRE

Carrillo Mateos, Juan Pablo; Carrillo Rivas, Belén

2000-01-01

La biología molecular constituye actualmente la base de la investigación biomédica. Gracias a la moderna técnica de transcripción inversa es posible obtener in Vitro proteínas humanas en gran cantidad. Un ejemplo de ello es la proteína morfogenética ósea recombinante humana (rhBMP), utilizada hasta ahora en forma experimental debido la disparidad de resultados observados en animales de experimentación y en humanos. Existen aún preguntas importantes que se deben responder antes de poder usar e...

Tallinn nimetas Poska stipendiumi saajad

Index Scriptorium Estoniae

2006-01-01

Tallinna linnavalitsus nimetas 10. mai istungil Jaan Poska stipendiumi saajad. Stipendium määrati kümnele Tallinna Tehnikaülikooli üliõpilasele : Eve Eenmaa, Andrus Räämet, Jelena Hartšenko, Andres Viia, Maksim Jenihhin, Raul Naadel, Martins Sarkans, Dmitri Šumigin, Külliki Tafel, Minna Varikmaa. Jaan Poska stipendium määratakse üliõpilasele silmapaistva ühiskondliku tegevuse eest Eesti ja Tallinna arengu heaks

Avaliação de vacinas recombinantes contra a leptospirose

OpenAIRE

Fagundes, Michel Quevedo

2012-01-01

A leptospirose é considerada um problema global para a saúde pública e veterinária. No Brasil, a enfermidade possui maior impacto em populações vulneráveis, as quais estão distribuídas nas favelas das grandes cidades, onde tradicionalmente ocorre elevada morbidade e mortalidade. Desta forma, torna-se necessário o estabelecimento de novas efetivas de intervenção para a redução dos casos. As vacinas disponíveis para a prevenção da enfermidade em humanos e animais são comprovadamente limitadas, ...

A somatotrofina bovina recombinante sobre a ovulação, condição corporal e níveis séricos de colesterol e glicose em ovinos Bovine recombinant somatotropin on ovulation, body condition score and cholesterol and glucose serum levels in sheep

Directory of Open Access Journals (Sweden)

Andréa Azevedo Pires de Castro

2002-06-01

Full Text Available O objetivo do presente estudo foi o de avaliar o efeito da somatotrofina bovina recombinante (BSTr sobre a taxa de ovulação após a indução, sobre o metabolismo intermediário do colesterol e da glicose em ovelhas, e no o ganho de peso de cordeiros lactentes cujas mães foram tratadas com BSTr bem como as variações do peso e escore corporal das mesmas. Utilizou-se para tanto 3mg/kg de BSTr em formulação de liberação prolongada em dose única para o primeiro experimento e, 4mg/kg para o segundo. No primeiro experimento, os resultados obtidos mostraram que a incidência de estro foi de 100% nos grupos controle e tratado, onde o número de corpos lúteos encontrados foi de 0,9 ± 0,18 no grupo controle e 1,18 ± 0,12 no grupo tratado, não sendo diferentes estatisticamente. Também não houve diferenças entre os grupos quanto aos níveis de colesterol e glicose. No experimento 2, houve uma diminuição na condição corporal das ovelhas do grupo tratado entre os dias 1 e 10 e seu aumento entre os dias 10 e 20, (pThe aim of the present study was to investigate if the rBST was able to improve ovulation rates in ewes syncronizated with progesterone, to verify its effects on cholesterol and glucose metabolism (experiment one and to evaluate weight gain in lactating ewes and their products (experiment two. Ewes were treated with 3mg/kg of rBST in the first experiment and 4mg/kg in the second. Ovulation rates were 0.9 ± 0.18 for the control group and 1.18 ± 0.12 for the treated group, and were not statisticaly different. Additionally, no differences between the groups were found in glucose and cholesterol serum levels in the first experiment. On the second experiment, body conditions scores in the treated group were decreased between days 1 to 10, then, increased between days 10 to 20 (p<0.05. Weight gain of lambs and ewes and body condition scores variations between days 1 and 20 were not different. In conclusion, rBST is not able to affect

Simulation of X-ray signals

International Nuclear Information System (INIS)

Weller, A.

1980-12-01

A parameterized form of the local emissivity is used for the simulation of soft X-ray signals obtained on the WENDELSTEIN W VII-A stellarator with a 30 diode array. Numerical calculation of the line integrals for the different viewing angles and for a set of rotation angles covering one full signal period provides simulated periodic signals. In addition radial profiles of the line integrated emmission averaged over some time interval or at specific times, the relative amplitude modulation and the relative phase of the oscillations are calculated. These have to be fitted to the corresponding measured signals and profiles in order to get a reliable picture of the local emissivity. The model can take into account two poloidally asymmetric contributions of the type m = 1,2,3 or 4 (m = poloidal mode number). Each asymmetry can be generated in two ways (modulation of intensity and of geometry parameters). Besides an uniform rotation of the asymmetric terms some specific simple time evolution of the signals can be included (non-uniform rotation, growth of oscillations, sawtooth oscillations). The various input parameters are illustrated and the result of a simulation procedure is presented for a particular discharge in W VII-A. (orig.)

Hamid Karzai on küll Afganistani riigipea, aga Massoud on kangelane / Leslie Leino

Index Scriptorium Estoniae

Leino, Leslie

2005-01-01

Afganistani valimistel võitsid opositsionäärid, tugevaim figuur nende hulgas on Ahmad Shah Massoudi kunagine kaasvõitleja Yunus Qanun, kelle siht on võõrväed riigist välja viia ja riik ühendada. Ameeriklased ja nende liitlased on ärevil, sest Qanun pole võõrvägede hulgas populaarne. Lisa: Põhimõtteliselt ameeriklaste vastu. Vt. samas: Afganistanis alustas pärast 30-aastast pausi tööd parlament

Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

Directory of Open Access Journals (Sweden)

Martina Bocchetta

2016-01-01

Conclusion: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing.

Kuni 10 kaitseväelast Malisse

Index Scriptorium Estoniae

2013-01-01

Valitsus saatis riigikokku eelnõu, mille kohaselt võib Eesti saata Euroopa Liidu väljaõppemissioonile Malis kuni 10 kaitseväelast. Kaitsevägi panustaks staabiohvitseridega, kelle peamiseks ülesandeks on osaleda Mali üksustele erinevate riikide poolt läbiviidava väljaõppe planeerimise ja nõustamise protsessides ning väljaõppemeeskonnaga, kelle ülesandeks on viia läbi Mali üksustele mitmesugust sõjalist väljaõpet

Utilization of high hydrostatic pressure for the study and refolding of proteins with quaternary structure

OpenAIRE

RODRIGUES, DANIELLA

2014-01-01

A produção de proteínas recombinantes é uma ferramenta essencial para a indústria biotecnológica e suporta a expansão da pesquisa biológica moderna. Uma variedade de hospedeiros pode ser utilizada para produzir estas proteínas e dentre eles, as bactérias E. coli são as hospedeiras mais utilizadas. No entanto, a expressão heteróloga de genes em E. coli frequentemente resulta em um processo de enovelamento incompleto que leva ao acúmulo de agregados insolúveis, conhecidos como corpos de inclusã...

Guía clínica de la enfermedad de Pompe de inicio tardío

OpenAIRE

Barba-Romero, Miguel A.; Barrot, Emilia; Bautista-Lorite, Juan; Gutiérrez-Rivas, E.; Illa, Isabel; Jiménez, Luis M.; Ley-Martos, Myriam; López de Munain, Adolfo; Pardo, Julio; Pascual-Pascual, Samuel I.; Pérez-López, Jordi; Solera, Jesús; Vílchez-Padilla, Juan J.

2012-01-01

Hasta 2006, la enfermedad de Pompe o glucogenosis tipo II era una enfermedad incurable y con tratamiento meramente paliativo. El desarrollo de la terapia de sustitución con la enzima α-glucosidasa recombinante humana ha constituido el primer tratamiento específico para esta enfermedad. El objetivo de esta guía es servir de referencia en el manejo de la variedad de inicio tardío de la enfermedad de Pompe, es decir, la que aparece después del primer año de vida. En la guía, un grupo de exper...

Generation and analysis of the immunogenicity of recombinant proteins based on different forms of the circumsporozoite antigen of Plasmodium vivax for the development of a universal vaccine against malaria.

OpenAIRE

Lais Helena Teixeira

2014-01-01

O P. vivax é a segunda espécie mais prevalente causadora de malária no mundo. Medidas de controle ineficientes exigem o desenvolvimento de novas estratégias de prevenção, como vacinas, novas drogas e novos inseticidas. O objetivo geral do trabalho foi gerar uma formulação vacinal universal com proteínas e adenovírus recombinantes capazes de induzir anticorpos contra as diferentes formas alélicas da proteína circumsporozoíta (CSP) do P. vivax. As proteínas foram produzidas em E. coli e purific...

Estrategia de verificación de calidad de las cepas de Escherichia coli conservadas en la Colección del Centro de Ingeniería Genética y Biotecnología

OpenAIRE

Iveldris Domínguez-Vázquez; Evelyn Olano-Ruiz; Angela Estela Sosa-Espinosa

2010-01-01

La colección de microorganismos de interés biotecnológico del Centro de Ingeniería Genética y Biotecnología incluye diferentes cepas de bacterias y levaduras utilizables en la manipulación de genes mediante el empleo de la ingeniería genética y para la producción de proteínas recombinantes por métodos biotecnológicos. La colección de hospederos de Escherichia coli centraliza todas las cepas que se utilizan en los proyectos de investigación-desarrollo de la institución. Este microorganismo con...

Influencia de la procedencia de los componentes del medio de cultivo en la calidad de los ensayos microbiológicos para la determinación de bacteriófagos

OpenAIRE

Annia González-Crespo; Angela E. Sosa-Espinosa

2017-01-01

La contaminación por virus bacterianos es uno de los problemas más difíciles de evaluar en la industria biotecnológica moderna, sobre todo en las producciones de proteínas que están basadas en cepas recombinante de Escherichia coli. Para certificar que un banco de cepas está libre de bacteriófagos el método más recomendado sigue siendo la inducción de la fase del ciclo lítico sobre placas con medios semisólidos. En este trabajo nos propusimos evaluar medios de cultivos elaborados con bases de...

Neutral transport calculations for W VII-X. First applications to W VII-X

International Nuclear Information System (INIS)

Sardei, F.

1988-01-01

Results of neutral gas transport calculations obtained with the DEGAS code are presented for a W VII-AS model plasma and a source of neutrals due to limiter recycling. For typical profiles of the plasma parameters as predicted for an ECRH discharge, the simulation yields a radial drop of the average neutral population by a factor of 30. The neutrals are strongly localized near the limiter and have a poloidal minimum at its opposite side. For a W VII-X configuration (HS4-12), a neutral source given by a high recycling ion flux equally distributed over the wall is considered. For an ion density of 5 x 10 1 3 /cc and 30 eV edge temperature, the neutrals originating from the wall completely ionize within the ergodic region. The corresponding average energy of cx neutrals hitting the wall is less than 30 eV. Neutral penetration into the plasma locally depends on the distance between wall and separatrix

Kuhu riiki oma firma masust taastuma viia? / Villi Tõntson

Index Scriptorium Estoniae

Tõntson, Villi, 1975-

2010-01-01

PricewaterhouseCoopersi ja Maailmapanga koostöös valminud maksukeskkondade võrdlevast uuringust "Paying Taxes 2010", kus üks hüpoteetiline ettevõte paigutati eri riikidesse ning seejärel reastati riigid vastavalt ettevõtte maksukoormusele, riiklike ja kohalike maksude hulgale ning maksude maksmiseks kulunud ajale. Graafik

Advances in hemophilia care: report of two symposia at the Hemophilia 2010 World Congress.

Science.gov (United States)

Dolan, Gerry; Cruz, Jussara Almeida; Steinhagen-Thiessen, Elisabeth; Kessler, Craig; Haaning, Jesper; Lemm, Georg; Altisent, Carmen; Guerrero, Caesar; Hermans, Cedric; Riske, Brenda; Bolton-Maggs, Paula

2012-04-01

The World Federation of Hemophilia (WFH) 2010 World Congress held in Buenos Aires, Argentina, in July 2010, attracted more than 4,300 participants from 106 countries. This report summarizes two symposia held during the congress. The first, titled "Emerging Co-Morbidities in the Aging Hemophilia Population: Healthcare Challenges and Treatment Opportunities," chaired by Gerry Dolan, MD, and Jussara Almeida Cruz, MD, examined the co-morbidities experienced by the aging hemophilic patient population, such as cardiovascular disease, cancer, arthritis, osteoporosis, hypertension, and obesity. In addition, Bayer's products in preclinical and clinical development were reviewed, including a novel factor VIIa variant and a long-acting factor VIII molecule, i.e., one that has undergone site-specific PEGylation (attachment of polyethylene glycol [PEG] polymer chains to another molecule). The other symposium, titled "Practical Steps to Making Better Care for Hemophilia Patients a Reality," chaired by Carmen Altisent, MD, and Cesar Guerrero, RN, reviewed the steps that hemophilia caregivers can take to improve the care of their patients. Issues such as the treatment of hemarthroses, the role of the research nurse, and the management of pediatric patients transitioning to adulthood were discussed.

Electron cyclotron emission measurements during 28 GHz electron cyclotron resonance heating in Wendelstein WVII-A stellarator

International Nuclear Information System (INIS)

Hartfuss, H.J.; Gasparino, U.; Tutter, M.; Brakel, R.; Cattanei, G.; Dorst, D.; Elsner, A.; Engelhardt, K.; Erckmann, V.; Grieger, G.; Grigull, P.; Hacker, H.; Jaeckel, H.; Jaenicke, R.; Junker, J.; Kick, M.; Kroiss, H.; Kuehner, G.; Maassberg, H.; Mahn, C.; Mueller, G.; Ohlendorf, W.; Rau, F.; Renner, H.; Ringler, H.; Sardei, F.; Weller, A.; Wobig, H.; Wuersching, E.; Zippe, M.; Kasparek, W.; Mueller, G.A.; Raeuchle, E.; Schueller, P.G.; Schwoerer, K.; Thumm, M.

1987-11-01

Electron cyclotron emission measurements have been carried out on electron cyclotron resonance heated plasmas in the WENDELSTEIN VII-A Stellarator. Blackbody radiation from the thermalized plasma main body as well as radiation from a small amount of weakly relativistic suprathermal electrons has been detected. In addition sideband emission has been observed near the second harmonic of the heating line source. Harmonic generation and parametric wave decay at the upper hybrid layer may be a reasonable explanation. (orig.)

The Impact of PERK on Post Traumatic Tauopathy in Alzheimer’s Disease

Science.gov (United States)

2017-10-01

neuronal cultures using EZNA total RNA Kit II according to manufacture instructions (Omega Bio -tek, catalog #R6934- 01). RNA was quantified using a...Expression probes for PSD-95 and GAPDH us- ing a ViiA 7 Real Time PCR System (Applied Bio - systems). PSD-95 expression was evaluated by normalizing to GAPDH as...interventions could be potential remedies for cellular dysfunction in chronic neurodegenerative disorders. Keywords: eIF2α, EIF2AK3, endoplasmic reticulum

Proceedings of US-Japan heliotron-stellarator workshop: Volume 2

International Nuclear Information System (INIS)

1987-01-01

This paper is the second of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the following: Ripple Transport at Arbitrary Collision Frequency, Transport Scaling in the Collisionless-Detrapping Regime, Transport Analysis for Heliotron E, Transport Analysis for ATF, Simulation Analysis of Heating and Transport, Analysis of W VII-A Data, Numerical Study of Fast Ion Confinement, Benchmarks of NBI Codes for Stellarators, ECH Commissioning and Plans for ATF, and ECH and ICH Startup Analysis

[Luuletused] / William Wordsworth ; tlk. Märt Väljataga

Index Scriptorium Estoniae

Wordsworth, William

2004-01-01

Sisu: Värsid, mis kirjutatud mõned miilid Tintern Abbeyst ülalpool... ; "Mõnd kirevahku kummalist..." ; "Käis vaikselt ojakalda peal..." ; "Kolm aastat sirguda ta võis..." ; "Mu hinge piiras unesulg..." ; "Kui mere taha viia ma..." ; Jugapuud. Saatesõna lk. 24. Orig.: Lines composed a few miles above Tintern Abbey... ; "Strange fits of passion have I known..." ; "She dwelt among the untrodden ways..." ; "Three years she grew..." ; "A slumber did my spirit seal..." ; "I traveled among unknown men..." ; Yew trees

Construcción de un vector para la integración cromosomal de un gen de fitasa de Bacillus licheniformis

Directory of Open Access Journals (Sweden)

Maria Teresa Fernández

2011-07-01

Full Text Available Las fitasas son una clase especial de fosfatasas que catalizan la hidrólisis secuencial del fitato. La incapacidad de las plantas para utilizar el fósforo a partir de los fitatos del suelo es debido a la baja actividad de fitasas en sus raíces. Los microorganismos del suelo juegan un importante papel en los procesos que afectan la trans- formación de los compuestos fosforados. Muchos de ellos pueden solubilizar el fósforo a partir de los fitatos, mediante la liberación de fitasas. Este proceso permite la movilización del fósforo hacia las plantas y un mejor aprovechamiento de este nutriente. Sin embargo, muchas bacterias carecen de los genes que codifican para estas enzimas, lo que disminuye la disponibilidad de este elemento en el suelo. Una alternativa es mejorar las rizobacterias en cuanto a su capacidad de solubilizar los fitatos del suelo, mediante la transformación genética. En este trabajo el gen phyL de Bacillus licheniformis fue clonado en el vector de liberación suicida pJMT6 (vector derivado del sistema pUT/mini Tn5. La construcción recombinante que contiene un marcador de selección no antibiótico, fue transformada en Escherichia coli CC118λpir. Un clon transformante (F16 fue seleccionado y posteriormente caracterizado. Estos resultados constituyen un primer paso para desarrollar rizobacterias promotoras del crecimiento mejoradas en cuanto a la producción de actividad fitasa recombinante, como alternativa para reducir la contaminación ambiental y mejorar la productividad de los cultivos.

Comportamiento reactogénico de la vacuna cubana contra la hepatitis B en niños física y mentalmente discapacitados

OpenAIRE

Plácido Pedroso Flaquet; Manuel Díaz González

2000-01-01

Se estudió la reactogenicidad de la vacuna recombinante cubana contra el virus de la hepatitis B, derivada de células de levadura (Heberbiovac-HB), al aplicar dosis de 5 y 10 mg y emplear el esquema de inmunización 0, una segunda dosis al mes y la tercera a los 6 meses a 2 grupos de niños física y mentalmente discapacitados de 5 a 14 años de edad. Los síntomas observados en el total de la población estudiada fueron de 5,1 %, mientras que en los grupos vacunados con 10 y 5 mg, la sintomatologí...

ALERGIA EN EL HUMANO INDUCIDA POR LA SALIVA DE INSECTOS DE LA FAMILIA CULICIDAE

Directory of Open Access Journals (Sweden)

Ligia Inés Moncada Álvarez

2011-04-01

Full Text Available Se hace una revisión de las moléculas que inoculan los insectos de la familia Culicidae al momento de la picadura y los mecanismos que muestran sus hospederos para contrarrestarlos y cómo algunas de esas moléculas, especialmente las enzimas se convierten en alérgenos que inducen una respuesta de amplio espectro, que va desde una pápula al momento de la picadura hasta una reacción anafiláctica. De la misma manera se analizan las posibilidades de diagnóstico con moléculas silvestres y antígenos recombinantes, lo mismo que pautas de tratamiento.

Utilización de la hormona de crecimiento en niños y adolescentes

OpenAIRE

Ignacio Bergadá

2013-01-01

El uso de la hormona de crecimiento en niños y adolescentes lleva más de cinco décadas. Desde el año 1985 se utiliza solamente hormona de crecimiento humana recombinante (rhGH). En la mayoría de los países el tratamiento con rhGH está indicado para el tratamiento de niños y adolescentes con deficiencia de hormona de crecimiento, síndrome de Turner, síndrome de Prader-Willi, insuficiencia renal crónica y niños nacidos pequeños para edad gestacional. El objetivo del tratamiento es mejorar el cr...

Produção de biofármacos pela levedura Pichia pastoris

OpenAIRE

Guerreiro, Diana de Jesus Leal Matos

2016-01-01

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz A produção comercial de biofármacos tem vindo a crescer desde a década de 70, altura em que a indústria biotecnológica se começou a aperfeiçoar exponencialmente. Atualmente, o mercado de produção de proteínas recombinantes atingiu valores multimilionários. Para a indústria biotecnológica, o objetivo é obter processos competitivos: altamente produtivos, para além de eficientes. Nas últimas d...

THE INFLUENCE OF SCIENCE LEARNING SET USING SCIENTIFIC APPROACH AND PROBLEM SOLVING MODEL ON LEARNING OUTCOMES OF JUNIOR HIGH SCHOOL STUDENTS IN THE SUBJECT OF HEAT AND TEMPERATURE

OpenAIRE

T. Triyuni

2016-01-01

This research aims to produce the scientific approach for science learning using a problem solving model on the topic of heat and temperatureon the junior high school learning outcome. The curriculum used during the study was curriculum 2013 (valid, practical and effective). The development of the learning setfollowed the four-D model which was reduced to three-D model (without dissemination). The study was tested in Class VIIA, VIIB, and VIIC in SMP Negeri 5 Academic Year 2015/2016. The data...

Samal teemal : kas karistus või võimalused? / Epp Rebane

Index Scriptorium Estoniae

Rebane, Epp, 1954-

2003-01-01

Vastukaja art.: Kala, Mairoos and Veskioja, Andrus. Klassist klassi määruse abil ... // Õpetajate Leht (2003) 30. mai.1996/1997. õa kehtima hakanud HM-i määrus nr 26 13. novembrist lubab klassikursuse kordajaid kas või kõigis ainetes puudulike hinnetega järgmisse klassi üle viia (kolmandaks aastaks samasse klassi jätta ei tohi). Selle tagajärjel suureneb iga aastaga klassikursuse kordajate ja järgmisse klassi üle viidavate õpilaste arv

Agenda 21 / Tiina Gaškov

Index Scriptorium Estoniae

Gaškov, Tiina

2000-01-01

Kuidas säästva eluviisi põhimõtteid ellu viia, sellega on tegelnud PHARE INTERREG õpilaste keskkonnaprojekt "3+3". Projekti elluviijateks olid koos Soome partneritega täiendusõppekeskuse Teave töörühm eesotsas Ene Kalmuse ja Karl Kaasikoviga. "3+3" tähendab, et koostööd, koolitust, kogemustevahetust hakkasid arendama kolm maakonda Eestist (Ida- ja Lääne-Viru- ning Jõgevamaa) ja Soomest Ita-Uusimaa, Kymenlaakso ja Päijät-Häme

The molecular genetics of Usher syndrome: Genetics of Usher syndrome

OpenAIRE

Ahmed, Zm; Riazuddin, S.; Riazuddin, S.; Wilcox, Er

2003-01-01

Association of sensorineural deafness and progressive retinitis pigmentosa with and without a vestibular abnormality is the hallmark of Usher syndrome and involves at least 12 loci among three different clinical subtypes. Genes identified for the more commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts fr...

Referendum Tšehhi Vabariigis / Helena Rögnerova

Index Scriptorium Estoniae

Rögnerova, Helena

2003-01-01

Ilmunud ka: Proceedings of the 9th international conference "Estonia and the European Union: Estonia on its way to a changing Europe" : October 30-November 1, 2002, Tallinn, Estonian National Library. - Tallinn, lk. 78-80. Tšehhi senati eurointegratsiooni komisjoni liikme arvates tuleks rahvani viia kaks sõnumit: EL on valmis looma ühesuguseid tingimusi nii praegustele kui uutele liikmetele ja EL-i liikmesriigina on tagatud neile traditsioonilised Euroopa väärtused nagu demokraatia, õigusriik, inimõiguste austamine ja vähemuste kaitsmine

Perekondade ühinemise eelnõust / Mart Nutt

Index Scriptorium Estoniae

Nutt, Mart, 1962-

2002-01-01

Ilmunud ka: Hiiumaa 1. apr. lk. 2, Meie Maa 13. apr. lk. 2, Põhjarannik, Severnoje Poberezhje 13. apr. lk. 2, Lääne-Harju Ekspress 13. apr. lk. 3, Lääne Elu, Vooremaa 16. apr. lk. 4;2, Molodjozh Estonii 18. apr. lk. 4, Sillamajeskii Vestnik : Notabene 18. apr. lk. 5, Valgamaalane 18. apr. lk. 2, Virumaa Teataja 30. apr. lk. 7. EL liikmeks saamisega kaasneb kohustus tagada turvalisus EL-i välispiiril ja viia ellu ühtset immigratsioonipoliitikat. Autor: Isamaaliit. Parlamendisaadik

Rong võib viia Tartust Tallinna kahe tunniga / Andres Reimer

Index Scriptorium Estoniae

Reimer, Andres

2004-01-01

Tartu-Tallinna rongid võivad 2005. aasta suvest hakata sõitma kuni 120 kilomeetrit tunnis. Tallinnast Tartusse saab senisest kiiremini aga alles pärast 2007. aastat, selleks investeerib raudtee aastatel 2006-2007 ligi 400 miljonit krooni

Eco-label - simple environmental choice / Andres Viia, Külliki Tafel

Index Scriptorium Estoniae

Viia, Andres

2003-01-01

Autorid selgitavad ökomärgistuse olemust ja vajalikkust tarbijate teavitamisel vähem keskkonda kahjustavatest toodetest ning teenustest. Lisatud näiteid regionaalsetest ja rahvuslikest ökomärkidest EL-is, tuntumatest ökomärkidest väljaspool Euroopat, hoiatavatest ja informatiivsetest keskkonnamärkidest ning libaökomärkidest. Vt. samas: North-East Estonia - a seat of an environment-friendly batteries' recycling

Juhan Parts soovib Res Publica tagasi tippu viia / Toomas Sildam

Index Scriptorium Estoniae

Sildam, Toomas, 1961-

2004-01-01

Res Publica esimees peaminister Juhan Parts plaanib minna oma erakonnaga kohalikele valimistele ning uurib võimalusi paremerakondade ühinemiseks. Rakveres toimunud erakonna üldkogust. Lisad: Peaministri neli rasket hetke; Res Publica ministrid said parteilt toetuse. Vt. samas: Reformierakond kiitis Res Publicat hea koostöö eest; Parts: 191 vastuhäält on hea tulemus

Trombolisis en el infarto agudo del miocardio en servicio de emergencias

Directory of Open Access Journals (Sweden)

Alexander del Toro Cámbara

2013-12-01

Full Text Available Introducción: las enfermedades cardiovasculares y dentro de estas, el infarto agudo del miocardio han sido el mayor problema de salud y la principal causa de muerte en muchos países del mundo durante varias décadas. Objetivo: determinar la efectividad de la estreptoquinasa recombinante cubana en la morbilidad y mortalidad del infarto agudo del miocardio. Material y método: se realizó una investigación observacional, descriptiva y transversal en los pacientes con diagnóstico de Infarto Agudo del Miocardio, que acudieron al servicio de emergencias del Policlínico Universitario Pedro Borrás, entre septiembre 2009 y agosto 2010. El universo lo integraron 56 pacientes con síndrome coronario agudo con elevación del ST, y la muestra 42 pacientes trombolizados. Las técnicas de procesamiento y análisis fueron la distribución en frecuencias absolutas y relativas y la prueba de ji cuadrado. Resultados: predominaron los pacientes del sexo masculino y edades comprendidas entre 45 y 60 años. Prevaleció la implantación del tratamiento por debajo de las seis horas, siendo tratados un número pequeño de pacientes durante la primera hora, efectiva en todos los casos. Sobresalieron como reacciones adversas la hipotensión arterial y las contracciones auriculares y ventriculares prematuras. Preponderó la desaparición del dolor y regresión de los cambios isquémicos electrocardiográficos como criterios de reperfusión. Conclusiones: el uso de la estreptoquinasa recombinante cubana contribuyó a disminuir la mortalidad en pacientes con infarto agudo al miocardio quedando así demostrado su efectividad.

Influence du cadmium (Cd++ sur l'activité biologique du récepteur des oestrogènes de la truite arc-en-ciel (Oncorhynchus mykiss

Directory of Open Access Journals (Sweden)

LE GUEVEL R.

1998-07-01

Full Text Available De nombreuses publications font l'état de l'action négative du cadmium (Cd++ sur la vitellogenèse chez les poissons. Le mécanisme d'action de ce métal n'étant pas clairement établi, une étude a été entreprise afin de déterminer si l'effet du cadmium passait par une action sur l'activité biologique du récepteur des oestrogènes de la truite arc-en-ciel (rtER. Cette étude a été réalisée dans un système de levures recombinantes, exprimant de manière stable rtER, et dans des hépatocytes de truite en culture primaire. Dans la levure, rtER activé par l'oestradiol (E2 contrôle spécifiquement l'expression d'un gène rapporteur codant pour l'enzyme ß-Galactosidase. Une concentration en Cd++ de 10 µM diminue de 45 % l'expression stimulée par l'oestradiol du gène rapporteur dans les levures recombinantes. De même, dans les hépatocytes, l'expression du gène de la vitellogénine (VTG, gène sous le contrôle positif de E2, est diminuée de 65 %. Le cadmium n'affecte pas la liaison de E2 à son récepteur et seule l'activité hormonodépendante est affectée par ce métal. Les résultats de cette étude montrent que l'effet négatif du cadmium sur l'action de l'oestradiol passe vraisemblablement par une action directe de ce métal sur la fonction de transactivation hormono-dépendante de rtER.

El análisis molecular y el inmunogénico sugieren la ausencia de las proteínas hidrofílicas de superficie en Leishmania (Viannia panamensis

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Marcel Marín

2008-09-01

Full Text Available Introducción. Los dos subgéneros en los cuales se divide el género Leishmania: Viannia y Leishmania, presentan diferencias significativas en las manifestaciones clínicas que causan, en su comportamiento de crecimiento en cultivos in vitro, en sus características genéticas y en la expresión de varias proteínas, entre ellas las de la familia hidrofílica de superficie superficie. Objetivo. Caracterizar las proteínas hidrofílicas de superficie en Leishmania (Viannia panamensis. Materiales y métodos. Se amplificaron los genes hasp en L. (V. panamensis usando cebadores específicos para la especie Leishmania (Leishmania major. Los productos de la amplificación fueron clonados, secuenciados y analizados con herramientas bioinformáticas. Posteriormente, se realizó un análisis serológico por medio de ensayo inmunoabsorbente ligado a enzimas y Western blot para detectar la presencia de anticuerpos específicos contra las proteínas hidrofílicas recombinantes de superficie de L. (L. major en sueros de pacientes con leishmaniasis de zonas endémicas de Colombia. Resultados. Se encontró una copia de un pseudogen en L. (V. panamensis, el cual presentó una identidad del 60% con el gen haspa de L. (L. major. Sólo se encontraron anticuerpos contra las proteínas recombinantes de superficie hidrofílicas en sueros de pacientes con leishmaniasis visceral. Conclusión. Estos resultados sugieren que no existe ninguna copia de un gen funcional hasp en L. (V. panamensis, lo que indica una pérdida de la familia de genes en esta especie de Leishmania perteneciente al subgénero Viannia.

Infecção pelo vírus da hepatite B em hemofílicos em Goiás: soroprevalência, fatores de risco associados e resposta vacinal Seroprevalence, vaccination response and risk factors for hepatitis B virus infection in hemophiliacs in Goiás

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Renato S. Tavares

2004-01-01

Full Text Available Objetivando determinar a prevalência da infecção pelo vírus da hepatite B (HBV em hemofílicos em Goiás, analisar os fatores de risco associados e avaliar a resposta vacinal contra hepatite B, 102 pacientes foram entrevistados e amostras sangüíneas coletadas para detecção dos seguintes marcadores sorológicos: HBsAg, anti-HBs e anti-HBc. Uma prevalência global de 43,7% (IC 95%: 33,5-54,2 para infecção pelo HBV foi encontrada. A análise multivariada dos fatores de risco mostrou que o número de episódios transfusionais e sorologia positiva para o vírus da hepatite C estiveram significantemente associados à positividade ao HBV. Foram identificados 49 (48,1% hemofílicos susceptíveis a esta infecção, sendo imunizados 30 pacientes com a vacina recombinante Euvax-B. Destes, 28 (93,3% indivíduos apresentaram títulos de anti-HBs maiores que 10 UI/L, o que mostra uma boa resposta à vacina. Os achados deste estudo ressaltam a importância das medidas de controle e prevenção da hepatite B nesta população.In order to study the prevalence and risk factors for hepatitis B in hemophiliacs in Goiás, 102 patients were interviewed and blood samples collected and screened for the following serological markers: HBsAg, anti-HBs and anti-HBc. An overall prevalence of 43.7% (95% IC: 33.5-54.2 was found to hepatitis B virus (HBV infection. Multivariate analysis of risk factors showed that the number of transfusions and positive serology for hepatitis C virus were significantly associated with HBV positivity. There were 48 (48.1% susceptible patients for this infection, of whom 30 were immunized with the Euvax-B vaccine. Among them, 28 (93.3% individuals developed anti-HBs titers higher than 10 IU/L. Thus, a good response was observed in the studied population. The findings of this study emphasize the importance of strategies of control and prevention of hepatitis B in this population.

A homozygous MYO7A mutation associated to Usher syndrome and unilateral auditory neuropathy spectrum disorder.

Science.gov (United States)

Xia, Hong; Hu, Pengzhi; Yuan, Lamei; Xiong, Wei; Xu, Hongbo; Yi, Junhui; Yang, Zhijian; Deng, Xiong; Guo, Yi; Deng, Hao

2017-10-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by sensorineural hearing loss, progressive visual loss and night blindness due to retinitis pigmentosa (RP), with or without vestibular dysfunction. The purpose of this study was to detect the causative gene in a consanguineous Chinese family with USH. A c.3696_3706del (p.R1232Sfs*72) variant in the myosin VIIa gene (MYO7A) was identified in the homozygous state by exome sequencing. The co‑segregation of the MYO7A c.3696_3706del variant with the phenotype of deafness and progressive visual loss in the USH family was confirmed by Sanger sequencing. The variant was absent in 200 healthy controls. Therefore, the c.3696_3706del variant may disrupt the interaction between myosin VIIa and other USH1 proteins, and impair melanosome transport in retinal pigment epithelial cells. Notably, bilateral auditory brainstem responses were absent in two patients of the USH family, while distortion product otoacoustic emissions were elicited in the right ears of the two patients, consistent with clinical diagnosis of unilateral auditory neuropathy spectrum disorder. These data suggested that the homozygous c.3696_3706del variant in the MYO7A gene may be the disease‑causing mutation for the disorder in this family. These findings broaden the phenotype spectrum of the MYO7A gene, and may facilitate understanding of the molecular pathogenesis of the disease, and genetic counseling for the family.

One amino acid in mouse activated factor VII defines its endothelial protein C receptor (EPCR) binding and modulates its EPCR-dependent hemostatic activity in vivo.

Science.gov (United States)

Pavani, G; Zintner, S M; Ivanciu, L; Small, J C; Stafford, K A; Szeto, J H; Margaritis, P

2017-03-01

Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the activated FVII (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) by using three substitutions from mouse PC (mPC), i.e. Leu4→Phe, Leu8→Met, and Trp9→Arg. The resulting molecule, mFVIIa-FMR, modeled the EPCR-binding properties of hFVIIa and showed enhanced hemostatic capacity in hemophilic mice versus mFVIIa. These data implied a role of EPCR in the action of hFVIIa in hemophilia treatment. However, the substitutions in mFVIIa-FMR only broadly defined the sequence determinants for its mEPCR interaction and enhanced function in vivo. Objectives To determine the individual contributions of mPC Phe4, Met8 and Arg9 to the in vitro/in vivo properties of mFVIIa-FMR. Methods The mEPCR-binding properties of single amino acid variants of mFVIIa or mPC at position 4, 8 or 9 were investigated. Results and conclusions Phe4 in mFVIIa or mPC was solely critical for interaction with mEPCR. In hemophilic mice, administration of mFVIIa harboring a Phe4 resulted in a 1.9-2.5-fold increased hemostatic capacity versus mFVIIa that was EPCR binding-dependent. This recapitulated previous observations made with triple-mutant mFVIIa-FMR. As Leu8 is crucial for hFVIIa-EPCR binding, we describe the sequence divergence of this interaction in

The effect of GlycoPEGylation on the physical stability of human rFVIIa with increasing calcium chloride concentration

DEFF Research Database (Denmark)

Plesner, Bitten; Westh, Peter; Hvidt, Søren

2011-01-01

The effects of calcium chloride on the structural, kinetic and thermal stability of recombinant human factor VIIa (rFVIIa) were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10 kDa PEG and a branched 40 kDa PEG, respectively. Three different CaCl(2......) concentrations were used: 10mM, 35 mM and 100mM. The secondary structure and tertiary structure of rFVIIa at 25C, measured by circular dichroism (CD), were maintained upon GlycoPEGylation as well as CaCl(2) content. In contrast, the thermal stability of the three rFVIIa compounds, measured by differential......FVIIa, whereas the concentration of CaCl(2) has to be raised to 100mM in order to see the same effect on the GlycoPEGylated rFVIIa compounds. The temperature of aggregation of rFVIIa, T(agg), increased as the CaCl(2) concentration increased from 35 mM to 100 mM, while T(agg) for the GlycoPEGylated r...

Clinical and Surgical Strategies for Avoiding or Reducing Allogeneic Blood Transfusions.

Science.gov (United States)

Dos Santos, Antonio Alceu; Baumgratz, Jose Francisco; Vila, Jose Henrique Andrade; Castro, Rodrigo Moreira; Bezerra, Rodrigo Freire

2016-04-01

Blood transfusions have still been used as a standard therapy to treat severe anemia. Current evidences point to both excessive allogeneic blood consumption and decreased donations, which result in reduced stocks in blood banks. Several studies have increasingly suggested a more restrictive transfusion practice for blood products. Currently, a number of autologous blood conservation protocols in surgeries have been noted. We report a case of severe anemia with 2.9 g/dL hemoglobin, which was successfully handled without using the standard therapy to treat anemia with hemotransfusions. Such a case of severe anemia condition resulted after the patient was submitted to ascending aortic aneurism repair, valvar aortic replacement, reimplantation of right coronary ostium, followed by a coronary artery bypass grafting and several postoperative complications. The main clinical and surgical strategies used in this case to avoid blood transfusions were acute normovolemic hemodilution, intraoperative blood cell salvage, and meticulous hemostasis, beyond epsilon-aminocaproic acid, desmopressin, prothrombin complex concentrate, human fibrinogen concentrate, factor VIIa recombinant, erythropoietin and hyperoxic ventilation.

Characterization of protein-DNA interactions in trypanosomes.

OpenAIRE

Ricardo Pariona Llanos

2014-01-01

O T. cruzi, é o agente causador da doença de Chagas. O estado redox NAD+/NADH intracelular é fundamental na manutenção do metabolismo celular. A GAPDH apresenta a função de proteção do telômero em mamíferos contra degradação, isto por causa de ligar se ao telômero. Aqui, mostramos que a GAPDH recombinante de T. cruzi (rTcGAPDH) interage com o DNA telomérico. A rTcGAPDH liga ao DNA de simples fita. Mostramos que a GAPDH liga ao DNA telomérico in vivo em células epimastigotas, onde a [NADH] é m...

Hemofilia A neonatal: reporte de un caso en Sincelejo (Colombia

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Jorge Mendoza-Herrera

2013-01-01

Full Text Available La hemofilia es una enfermedad hemorrágica hereditaria caracterizada por la deficiencia funcional o cuantitativa del factor VIII (hemofilia A o del factor IX (hemofilia B de la coagulación. El diagnóstico de la hemofilia es eminentemente clínico; situación clave que ofrece una ventana de oportunidad para que el médico de primer nivel de atención esta - blezca un diagnóstico oportuno y eficiente. Los datos clínicos de los dos tipos de hemofilia son sustancialmente idénticos y varían solo en relación con el grado de la deficiencia. En este trabajo se describe un caso de un recién nacido que presentó un hematoma como consecuencia de una venopunción. El paciente presentó prolongación en el tiempo parcial de tromboplastina y una disminución del Factor VIII de la coagulación, confirmándose el diagnóstico de hemofilia A. Se inició tratamiento con factor VIII recombinante y el paciente presentó una gran mejoría de cuadro clínico. Este trabajo tiene como objetivo alertar al cuerpo médico sobre la importancia de conside - rar esta enfermedad dentro del diagnóstico diferencial en los síndromes hemorrágicos del recién nacido, incluso sin la existencia de antecedentes famili ares. El tratamiento apropiado generará un impacto positivo en la salud de los pacientes y su familia, reduciendo con ello las complicaciones, costos por hos pitalización y muerte.

Usefulness of recombinant human TSH-aided radioiodine doses administered in patients with differentiated thyroid carcinoma Administración de dosis terapéuticas de radioyodo luego de TSH recombinante en pacientes con carcinoma diferenciado de tiroides

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Fabián Pitoia

2006-04-01

Full Text Available The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC. In order to establish the efficacy of RI therapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17, with previous thyroid bed uptake and undetectable thyroglobulin (Tg levels under levothyroxine treatment and GII (n=11, with proven metastatic local or distant disease. Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months. Sixteen patients (94% in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer and five out of the remaining patients have persistent disease. In conclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94% patients (GI. rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels.Los estudios publicados que confirman la seguridad y eficacia de la TSH recombinante (rhTSH llevaron a un incremento en el interés para su uso como adyuvante terapéutico en el CDT (ablación o tratamiento

Emerging treatment strategies for trauma-induced coagulopathy.

Science.gov (United States)

Sorensen, B; Fries, D

2012-01-01

Trauma-induced coagulopathy has a multifactorial aetiology. Coagulopathy is related to blood loss including consumption of clotting factors and platelets and haemodilution. Additionally hyperfibrinolysis, hypothermia, acidosis and metabolic changes affect the coagulation system. This is a review of pathophysiology and new treatment strategies for trauma-induced coagulopathy. Paradigms are actively changing and there is still a shortage of data. The aim of any haemostatic therapy is to control bleeding and minimize blood loss and transfusion requirements. Transfusion of allogeneic blood products as well as trauma-induced coagulopathy cause increased morbidity and mortality. Current opinion is based on present studies and results from small case series, combined with findings from experimental studies in animals, in vitro studies and expert opinions, as opposed to large, randomized, placebo-controlled studies. A summary of new and emerging strategies, including medical infusion and blood products, to beneficially manipulate the coagulation system in the critically injured patient is suggested. Future treatment of trauma-induced coagulopathy may be based on systemic antifibrinolytics, local haemostatics and individualized point-of-care-guided rational use of coagulation factor concentrates such as fibrinogen, prothrombin complex concentrate, recombinant factor VIIa and factor XIII. The authors speculate that timely and rational use of coagulation factor concentrates will be more efficacious and safer than ratio-driven use of transfusion packages of allogeneic blood products. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Associação entre proteínas do plasma seminal, motilidade e viabilidade espermática em coelhos submetidos a doping genético Association among seminal plasma proteins, sperm motility and sperm viability in rabbits submitted to gene doping

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G Urtiaga

2013-02-01

Full Text Available Neste trabalho foi estudada a correlação entre o perfil proteico do plasma seminal e a motilidade e viabilidade espermática em coelhos submetidos ao tratamento com vetores de expressão contendo o gene da eritropoetina (EPO e com EPO recombinante humana. Foram identificadas, em coelhos submetidos ao tratamento com vetor de DNA contendo o gene da EPO, duas bandas proteicas associadas a alterações na motilidade espermática - 48kDa à baixa motilidade (PIn this study the correlation between seminal plasma protein profile and the sperm motility and sperm viability in rabbits submitted to treatment with an expression vector containing EPO gene and with human recombinant EPO was evaluated. In rabbits submitted to treatment with EPO expression vector, two protein bands were associated to sperm motility - 48kDa associated to low motility (P<0.05 and 18kDa to high motility (P<0.05 - and this protein band was also associated to high sperm viability (P<0.05. In rabbits submitted to treatment with human recombinant EPO, a protein factor, 63kDa, was associated to high sperm motility (P<0.05 while two protein factors, 26 and 40kDa, were associated to high sperm viability (P<0.05. These results suggest that gene doping leads to changes in rabbit seminal plasma protein, altering sperm motility and sperm viability.

Comparação entre diversos antígenos para o diagnóstico de Anaplasma marginale por ELISA Comparison between several antigens for diagnosis of Anaplasma marginale by ELISA

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Carlos A.N. Ramos

2010-01-01

Full Text Available Anaplasmose bovina é uma doença com grande importância nas regiões tropicais e subtropicais do mundo por determinar perdas econômicas devido à mortalidade e redução da produtividade. É causada por Anaplasma marginale, uma riquétsia intraeritrocítica obrigatória cujo controle requer, além de uma vacina eficiente, uma acurada identificação de bovinos cronicamente infectados. Apesar de existirem atualmente diversos métodos de diagnóstico dessa riquétsia, os métodos sorológicos, em particular o ensaio de imunoadsorção enzimática-ELISAs, são os mais utilizados devido à sua versatilidade e praticidade. No entanto, devido ao grande número de antígenos disponíveis, atualmente torna-se necessária uma avaliação para definir quais antígenos apresentam um melhor desempenho no diagnóstico da anaplasmose. Soros de bovinos positivos e negativos para A. marginale por PCR, e soros de animais provenientes do Brasil e Costa Rica, foram testados em ELISAs baseados em MSP1a, MSP2 e MSP5 recombinantes, um pool das três proteínas recombinantes, e antígeno de lisado de corpúsculos iniciais da riquétsia (CI. Utilizando soro de bovinos positivos para A. marginale por PCR, uma maior sensibilidade foi observada no ELISA CI. No entanto, uma maior especificidade, com soro de bovinos negativos a PCR, foi observada com os ELISAs recombinantes. O porcentual de bovinos positivos do Brasil e Costa Rica foi maior com ELISA CI. Razões para essas diferenças são discutidas.Bovine anaplasmosis is a major disease in tropical and subtropical regions of the world by determine economical loss due mortality and productive reduction. The disease is caused by Anaplasma marginale, an intraerythrocytic rickettsia whose control requires, besides an efficient vaccine, the accurate identification of chronically infected cattle. Although the existence of diverse methods of diagnosis of this rickettsia, the serological methods, in particular the enzyme

Construção de uma biblioteca de fragmentos de anticorpos monoclonais de galinhas com cadeia única (scFv por phage display com reatividade cruzada para estirpes heterólogas do vírus da bronquite infecciosa aviária Construction of an avian single chain monoclonal antibodies (scFv library by phage display that cross-reacted with heterologous avian infectious bronchitis virus strains

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Camila Cesário Fernandes

2010-06-01

Full Text Available Anticorpos monoclonais constituem a base de vários testes usados na detecção e na identificação de antígenos. Nesse contexto, tais imuno-reagentes têm sido extensivamente empregados na identificação de estirpes virais envolvidas na etiologia de surtos de bronquite infecciosa a campo, permitindo o aperfeiçoamento das técnicas de detecção e caracterização antigênica do vírus da bronquite infecciosa das galinhas (VBI. No presente estudo, uma biblioteca de fragmentos de anticorpos de galinha originalmente preparada por phage display contra a estirpe vacinal (H120 do VBI foi usada para a seleção de fragmentos de anticorpos recombinantes com reatividade cruzada para as estirpes heterólogas IBVPR01 e IBVPR05, isoladas de surtos a campo no Brasil e a estirpe SE-17, isolada nos Estados Unidos. Após três ciclos de panning, foi identificado, pelo ELISA, um conjunto de 15 anticorpos scFv expressos em fagos e com reatividade cruzada para essas mesmas estirpes do VBI. A análise por Western-blotting revelou que dois desses clones apresentavam fagos expressando fragmentos de anticorpos monoclonais com reatividade cruzada para a nucleoproteína N das três estirpes do VBI e também para a forma recombinante dessa nucleoproteína derivada da estirpe M41. Concluindo, os fragmentos de anticorpos monoclonais recombinantes scFv-N produzidos em fagos interagem com um epítopo mais conservado da proteína N do VBI e apresentam um grande potencial para utilização na detecção e no diagnóstico direto desse vírus.Monoclonal antibodies are the basis of various techniques used for antigen detection or characterization, and their use is specially recommended for the identification of viral strains involved in the etiology of infectious bronchitis outbreaks. These antibodies are homogeneous, highly specific and fully characterizable, allowing the improvement of immunological techniques detection and antigenic characterization of avian infectious

Development and evaluation of a recombinant DNA vaccine candidate expressing porcine circovirus 2 structural protein Desenvolvimento e avaliação de um candidato à vacina de DNA recombinante expressando a proteína estrutural do circovírus suíno

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Abelardo Silva Júnior

2009-01-01

Full Text Available Porcine circovirus 2 (PCV2 is generally associated with the porcine circovirosis syndrome, which is considered an important disease of swine and has potentially serious economic impact on the swine industry worldwide. This article describes the construction of a recombinant plasmid expressing the PCV2 structural protein and the evaluation of cellular and humoral immune responses produced by this recombinant vaccine in BALB/c mice. The vaccine candidate was obtained and analyzed in vivo, in an effort to determine the ability to induce a specific immune response in mice. DNA was extracted from a Brazilian PCV2 isolate and the gene coding for Cap protein was amplified by PCR and inserted into an expression plasmid. Groups of BALB/c mice were inoculated intra-muscularly and intradermally in a 15-day interval, with 100 µg and 50 µg of the vaccine construct, respectively. Another group was inoculated intramuscularly with 100 µg of empty plasmid, corresponding to the control group. Seroconversion and cellular response in BALB/c mice were compared and used for vaccine evaluation. Seroconversion was analyzed by ELISA. After a series of 3 immunizations the spleen cells of the immunized animals were used to perform lymphocyte proliferation assays. Seroconversion to PCV2 was detected by ELISA in the animals inoculated with the vaccine construct when compared with control groups. Lymphocyte proliferation assays showed a stronger cell proliferation in the inoculated animals compared with the control group. Thus, the vaccine candidate construct demonstrated to be able to induce both humoral and cellular responses in inoculated mice.O circovírus suíno 2 (PCV2 é geralmente associado à síndrome da circovirose suína, que é considerada uma importante doença de suínos e possui um sério impacto econômico na suinocultura mundial. Este trabalho descreve a construção de um plasmídeo recombinante que expressa a proteína estrutural do PCV2 e a avalia

Desarrollo de agentes inmunizantes contra el dengue

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Francisco J. López Antuñano

2000-05-01

Full Text Available El complejo de los cuatro flavivirus del dengue es transmitido principalmente por el mosquito Aedes aegypti. Se han atribuido epidemias a la actividad de A. albopictus, A. polynesiensis y a varias especies del complejo A. scutellaris. Los factores de riesgo que determinan la probabilidad de enfermar o morir por dengue están relacionados tanto con el huésped (características genéticas, estado inmunitario, forma de vida y condiciones de salud, saneamiento básico de la vivienda y abastecimiento de agua potable como con el virus (variabilidad genética de cepas entre y dentro de los serotipos, diferente capacidad patógena y distribución geográfica. A pesar de la falta de conocimiento sobre la inmunobiopatología del dengue, se han hecho importantes avances para conseguir una respuesta inmunitaria protectora con virus atenuados y con antígenos obtenidos por medio de tecnologías recombinantes. Desde los años 40, se ha intentado desarrollar vacunas contra el dengue. La inmunidad que se adquiere por infección natural es específica para cada serotipo y se han documentado infecciones por tres serotipos diferentes en la misma persona, por lo que probablemente sea necesaria una vacuna tetravalente. En voluntarios se han probado vacunas contra los cuatro serotipos que han sido inmunógenas y seguras. Aunque las vacunas con virus atenuados son prometedoras, son necesarios nuevos estudios sobre su eficacia y seguridad. Actualmente están en curso estudios para producir vacunas contra el virus del dengue mediante tecnologías de ADN recombinante y otras técnicas de biología molecular, utilizando como antígenos proteínas estructurales (principalmente la glicoproteína E y no estructurales. Con el mismo propósito se han usado varios vectores de expresión, como Escherichia coli, baculovirus, virus de la vacuna y virus de la fiebre amarilla. Lamentablemente, no se han obtenido resultados satisfactorios en el hombre. La necesidad de desarrollar

On modular stellarator reactor coils

International Nuclear Information System (INIS)

Rau, F.; Harmeyer, E.; Kisslinger, J.; Wobig, H.

1985-01-01

Modular twisted coils are discussed which produce magnetic fields of the Advanced Stellarator WENDELSTEIN VII-AS type. Reducing the number coils/FP offers advantage for maintenance of coils, but increases the magnetic ripple and B m /B o . Computation of force densities within the coils of ASR and ASB yield local maximum values of about 80 and 180 MN/m 3 , respectively. A system of mutual coil support is being developed. Twisted coils in helical arrangement provide a reactor-sized HELIAC system. In order to reduce the magnetic ripple, a large number of 14 coils/FP in special arrangement is used

ORMEC: a three-dimensional MHD spectral inverse equilibrium code

International Nuclear Information System (INIS)

Hirshman, S.P.; Hogan, J.T.

1986-02-01

The Oak Ridge Moments Equilibrium Code (ORMEC) is an efficient computer code that has been developed to calculate three-dimensional MHD equilibria using the inverse spectral method. The fixed boundary formulation, which is based on a variational principle for the spectral coefficients (moments) of the cylindrical coordinates R and Z, is described and compared with the finite difference code BETA developed by Bauer, Betancourt, and Garabedian. Calculations for the Heliotron, Wendelstein VIIA, and Advanced Toroidal Facility (ATF) configurations are performed to establish the accuracy and mesh convergence properties for the spectral method. 16 refs., 13 figs

Fusion machine shows first inclination to act as a reactor

International Nuclear Information System (INIS)

Brever, R.

1980-01-01

The author reports recent work by the Max-Planck Institut fur Plasmaphysik (IPP) in Garching (West Germany) on their series of Stellarator-type experiments. In the latest (Wendelstein VII-A) the tokamak principle is used only for the initial heating of the plasma, energy being supplied subsequently by neutral particle injection. It has proved to be possible to reduce the tokamak heating current to almost zero while achieving a particle density of 10 14 /cm 3 and peak temperatures of 10 7 degrees. The prospect of a continuously operating Stellarator-type reactor appears therefore to be opened up. (C.J.O.G.)

IPP annual report 1981

International Nuclear Information System (INIS)

1982-01-01

In part A of this annual report the tokamak and stellarator projects at the IPP are reported: ASDEX, ASDEX upgrade, JET collaboration, NET collaboration, Wendelstein VII-7, Wendelstein VII-AS, Wendelstein VII-X and stellarator reactor system studies. In part B the departments and research groups give a brief, but detailed report of the results in the field of research and development. In part C a review is presented of the IPP organisation. Part D includes the papers and conference reports published in 1981. Finally a brief description of the IPP projects at German universities is presented. (GG) [de

Expresión y purificación de las proteínas estructurales del rotavirus VP5* y VP8* en bacterias E. coli BL21(DE3

Directory of Open Access Journals (Sweden)

Luz Yurany Moreno

2013-01-01

Full Text Available Título en ingles: Expression and purification of rotavirus structural proteins VP5* and VP8* in bacteria E. coli BL21(DE3 Resumen La caracterización de las proteínas estructurales del rotavirus y de las proteínas de la superficie de la célula hospedera implicadas en la unión y penetración del virion requiere de la disponibilidad de cantidades suficientes y de alto grado de pureza de estas proteínas.  Por lo tanto, el objetivo de este trabajo fue expresar y purificar las proteínas estructurales del rotavirus de la cepa RRV, VP5* y VP8*, y producir anticuerpos policlonales dirigidos contra ellas. Se expresaron las proteínas recombinantes VP5* (rVP5* y VP8* (rVP8* en bacterias E. coli BL21(DE3 transfectadas con el plásmido pGEX-4T que contenía sus secuencias codificantes. Se consideraron como variables el medio de crecimiento, número de bacterias antes de inducir la expresión, concentración del inductor y tiempo de inducción. La mayor proporción de rVP8* se obtuvo cuando las bacterias transformadas se cultivaron en medio LB y la inducción se llevó a cabo con 1 mM de IPTG cuando el cultivo alcanzó una OD 600 nm de 0.5 y la inducción se mantuvo durante 6 h. rVP5* alcanzó la mayor proporción cuando células a una OD 600 nm de 0.2 fueron inducidas con 0.5 mM de IPTG durante 4 h en medio 2XYT en presencia de glucosa al 2 %. Las proteínas recombinantes obtenidas, acumuladas en la fracción insoluble, fueron solubilizadas con detergentes iónicos y no iónicos, seguido de purificación mediante cromatografía de afinidad antes de ser empleadas como antígenos para la producción de anticuerpos policlonales en conejos. Estos anticuerpos se caracterizaron mediante su capacidad de reconocimiento de los antígenos correspondientes en ELISA, “Western blotting”, y en ensayos de inmunocitoquímica en células infectadas con rotavirus RRV. La cantidad y el grado de pureza de las proteínas recombinantes obtenidas, y los anticuerpos

On see realistlik - 400 ehitust kahe suvega ellu viia? / Raimo Poom

Index Scriptorium Estoniae

Poom, Raimo

2011-01-01

CO₂ kvoodi müügist rahastatakse üle 400 objekti energiasäästlikumaks renoveerimist. Ehitusettevõtjate liidu tegevdirektori Indrek Petersoni hinnangul töö firmade taha ei jää, pigem nähakse probleemi hankeprotsesside korraldamises ning projekteerimishangete läbiviimises

Factor de crecimiento semejante a la insulina tipo I (IGF-I y cirrosis hepática Insulin-like growth factor I (IGF-I and liver cirrhosis

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M. Conchillo

2007-03-01

Full Text Available El factor de crecimiento semejante a la insulina tipo I (IGF-I es una hormona polipeptídica segregada en múltiples tejidos por efecto de la hormona de crecimiento (GH. Es responsable de parte de las acciones de la GH y además tiene efecto hipoglucemiante y anabolizante. El 90% del IGF-I circulante es de origen hepático y ejerce efectos autocrinos, paracrinos y endocrinos, estos últimos en múltiples tejidos. En la cirrosis hepática se produce una disminución progresiva de la producción hepática de IGF-I que llega a ser indetectable en la enfermedad avanzada. Algunas de las complicaciones de la cirrosis, fundamentalmente nutricionales y metabólicas (resistencia a insulina, desnutrición, osteopenia, hipogonadismo, alteraciones intestinales podrían estar, al menos en parte, relacionadas con esta carencia de IGF-I dado que algunas acciones de IGF-I representan la imagen inversa de las complicaciones de la cirrosis. A pesar de ello, nunca se había propuesto tratamiento sustitutivo con IGF-I en la cirrosis. En una serie de estudios experimentales realizados en ratas cirróticas se demostró que el tratamiento con dosis bajas de IGF-I recombinante produce dos tipos de efectos en la cirrosis experimental: a mejoría del hígado, dado que mejora la función hepatocelular, la hipertensión portal y la fibrosis hepática; y b mejoría de las alteraciones extrahepáticas de la cirrosis dado que mejora la eficiencia del alimento ingerido, la masa muscular, la masa ósea, la función y estructura gonadales y la función y estructura intestinales con normalización de la malabsorción de azúcares y aminoácidos y la mejoría de la función intestinal de barrera manifestada por disminución de la endotoxemia y la translocación bacteriana. Posteriormente el primer ensayo clínico piloto, aleatorizado, doble ciego y controlado con placebo llevado a cabo en un número reducido de pacientes cirróticos demostró aumento de la albúmina sérica y

Consensus recommendations for preventing and managing bleeding complications associated with novel oral anticoagulants in singapore.

Science.gov (United States)

Ng, Heng Joo; Chee, Yen Lin; Ponnudurai, Kuperan; Lim, Lay Cheng; Tan, Daryl; Tay, Jam Chin; Handa, Pankaj Kumar; Akbar Ali, Mufeedha; Lee, Lai Heng

2013-11-01

Novel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished. A working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified. The NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required. NOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

Successful surgical repair of acute type A aortic dissection without the use of blood products.

Science.gov (United States)

Papalexopoulou, N; Attia, R Q; Bapat, V N

2013-10-01

We report successful surgical treatment of type A aortic dissection in a Jehovah's Witness without the use of any blood products. An interposition graft replacement of the ascending aorta was carried out. This was under right axillo-atrial cardiopulmonary bypass with antegrade cerebral perfusion via right a subclavian and left carotid cannula for 24 minutes at 28°C. Body temperature was kept at 32°C throughout. Autologous transfusion was deployed using cell salvage and a preoperative haemodilution technique. The patient was given tranexamic acid, desmopressin, recombinant factor VIIa, folic acid and epoetin alfa. Patients who object to transfusion represent a significant challenge, especially those who are at a high risk of coagulopathy associated with inherent aortic dissection leading to perturbed haemodynamics, cardiopulmonary bypass and hypothermic circulatory arrest. Type A aortic dissection repair is possible in patients refusing the use of blood products with blood salvage techniques and synthetic products that can limit the risk of bleeding. Minimal hypothermia is vital to preserve platelet function and avoid coagulopathy. Thus, a combination of normothermic/minimal hypothermia and antegrade cerebral protection with a blood conservation strategy can be deployed for a successful surgical outcome in aortic dissection without transfusion.

Caracterización bioquímica de la enzima bifuncional dihidrofolato reductasa-timidilato sintasa de Leishmania (Viannia y su evaluación como blanco molecular

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Edison Osorio

2013-09-01

Full Text Available Introducción. La dihidrofolato reductasa (DHFR se ha utilizado como blanco molecular en tratamientos antibacterianos, anticancerígenos y antipalúdicos. También, actúa como blanco molecular en Leishmania; sin embargo, no existen reportes de la enzima bifuncional en especies de Leishmania (Viannia. Materiales y métodos. Se ha aislado y expresado en Escherichia coli el gen que codifica para la enzima bifuncional DHFR y la timidilato-sintasa (TS de Leishmania braziliensis. La enzima recombinante se purificó y caracterizó, y se evaluó el efecto inhibitorio de algunos antifolatos, así como de cuatro alcaloides aporfínicos. Resultados. El gen se compone de aproximadamente 1.560 pb y codifica un péptido de 58 kDa que contiene los dominios DHFR y TS ligados en una sola cadena polipeptídica. La enzima recombinante DHFR-TS, utilizando el dihidrofolato (H2F como sustrato, presentó valores de Km y Vmax de 55,35± 4,02 (media ± el error estándar de la media y de 0,02 ± 5,34 x 10-4, respectivamente. La enzimar DHFR-TS de L. braziliensis presentó valores de Ki para los antifolatos en el rango de micras. El metotrexato fue el inhibidor más potente de la actividad enzimática (Ki=22,0 mM en comparación del trimetoprim (Ki=33 mM y la pirimetamina (Ki=68 mM. Estos valores de Ki son significativamente más bajos en comparación con los obtenidos para los alcaloides aporfínicos. Conclusión. Los resultados muestran el efecto inhibitorio de los antifolatos sobre la actividad enzimática, lo cual indica que la rDHFR-TS de L. braziliensis podría ser un modelo para estudiar moléculas antiprotozoarias potenciales. doi: http://dx.doi.org/10.7705/biomedica.v33i3.1434

Clonagem e purificação de fragmento da proteína capsidial de Banana streak OL virus Cloning and purification of Banana streak OL virus coat protein fragment

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Ricardo Lombardi

2010-08-01

Full Text Available O objetivo deste trabalho foi clonar e induzir a expressão de fragmento da proteína capsidial de Banana streak OL virus (BSOLV-CP em Escherichia coli, bem como purificar a proteína recombinante obtida. Empregou-se um par de iniciadores específicos para amplificar, em PCR, um fragmento de aproximadamente 390 pb, da região codificadora da porção central da BSOLV-CP. O fragmento obtido foi clonado em vetor pGEM-T Easy, subclonado em vetor pQE-30 e transformado em células de E. coli M15 (pREP4 por choque térmico. A expressão da proteína foi induzida por tiogalactopiranosídeo de isopropila (IPTG, e a proteína recombinante BSOLV-rcCP de 14 kDa foi detectada em Western blot e Dot blot. A expressão da proteína BSOLV-rcCP abre novas possibilidades para a obtenção de antígenos para a produção de antissoros contra o BSOLV.The objective of this work was to clone and to induce the expression of a fragment of Banana streak OL virus coat protein (BSOLV-CP in Escherichia coli, as well as to purify the obtained recombinant protein. Two specific primers were used for the PCR-amplification of approximately 390-bp fragment of the codifying region of the BSOLV-CP central portion. The obtained fragment was cloned in pGEM-T Easy vector, subcloned in pQE-30 expression vector and transformed into competent E. coli M15 (pREP4 cells by heat shock. The protein expression was induced by isopropyl thiogalactopyranoside (IPTG and the 14-kDa BSOLV-rcCP recombinant protein was detected in Western and Dot blotting. The expression of the BSOLV-rcCP protein enables new approaches to the obtention of antigens for the antisera production against BSOLV.

Expresión de toxinas activas para larvas de mosquito por una cepa nativa de Asticaccaulis excentricus

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Sergio Ordúz

2000-02-01

Full Text Available

El control de mosquitos con insecticidas biológicos, como las toxinas producidas por especies del género Bacillus ha sido usado ampliamente en muchos países. Sin embargo, la rápida sedimentación de éstas las coloca fuera del alcance de la zona de alimentación de las larvas de mosquito. Con el propósito de resolver este problema se ha propuesto clonar los genes de dichas toxinas en bacterias acuáticas que son capaces de vivir y multiplicarse en la parte superior de la columna de agua, donde se alimentas los mosquitos anofelinos. Se escogieron dos cepas de la bacteria acuática Asticaccaulis excentricus para expresar los genes de la toxina binaria de B. sphaericus y el gen cry11Bb de B. thuringiensis subesp. Medellín clonados en un vector de expresión adecuado. En experimentos de alimentación se encontró que larvas de las especies Culex quinquefasciatus, Aedes aegypti y Anopheles albimanus fueron capaces de sobrevivir en una dieta basada exclusivamente en esta bacteria gram negativa. Las células de A. excentricus recombinante fueron capaces de expresar ambos genes, pero solamente la cepa expresando los genes de la toxina binaria de B. sphaericus fue tóxica para larvas de mosquito. Extractos de proteasas de A. excentricus no degradaron la toxina Cry11Bb, lo que indica que es otro el mecanismo que interfiere con la expresión de la toxicidad de la toxina Cry11Bb en esta bacteria recombinante. Los experimentos de flotación mostraron que A. excentricus recombiante se mantiene en la parte superior de la columna de agua al igual que las cepas nativas, y por más tiempo que las cepas de Bacillus.

Gangrena de Fournier Fournier's gangrene

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Gabriel González Sosa

2010-09-01

Full Text Available Se presenta el caso de un paciente con gangrena de Fournier o fascitis necrosante. Después de su ingreso en la Unidad de Cuidados Intensivos se le realizó tratamiento quirúrgico precoz (incisión y drenaje amplio de toda la zona afectada así como desbridamiento de la zona de necrosis; se tomó muestra de pus para estudio microbiológico y se comenzó tratamiento antibiótico de inmediato (ceftriaxona, amikacina y metronidazol. Se identificaron como agentes causantes del proceso Pseudomonas aeruginosa y Escherichia coli (sensibles a la ceftriaxona y la amikacina. Como tratamiento coadyuvante, se aplicaron 10 sesiones de cámara hiperbárica y 12 dosis de factor de crecimiento humano recombinante liofilizado, que se infiltraron en el interior de la zona quirúrgica para contribuir al cierre por tercera intención.This is the case of a patient presenting with Fournier gangrene of necrotizing fasciitis. After admission in Intensive Care Unit (ICU he undergoes an early surgical treatment (incision and wide drainage of the whole involved zone as well as debridement of necrosis zone; a pus sample was took for microbiologic study and a immediate antibiotic treatment was started (Ceftriaxone, Amikacin and Metronidazole. Pseudomonas aeruginosa and Escherichia coli (sensitive to Ceftriaxone and Amikacin were identified as the causative agents of process. As adjuvant treatment ten sessions of hyperbaric chamber were applied and twelve dose of lyophilized recombinant human growth factor with infiltration into the surgical zone for the third intention closure.

Extension model of lactation curves to evaluate the effect of the recombinant bovine somatotropin on milk yield in Holstein cows Modelo de extensão de curvas de lactação para avaliar o efeito da somatotropina bovina recombinante sobre a produção de leite em vacas Holstein

Directory of Open Access Journals (Sweden)

A. Palacios-Espinosa

2010-02-01

Full Text Available An extension model of lactation curves was used to determine the effect of recombinant bovine somatotropin (bST-r on milk yield in Holstein dairy cattle. This model use the fitted values obtained by the Wood model, and was tested on the records of 66 cows. The milk yield predicted with the extension model and the observed yield were compared and no significant differences were observed (P>0.05. Once the extension model was validated, the milk yield tests of 199 cows were used. The cows received bST-r 500mg by subcutaneous injections. The injections were applied after 100 days in milk at 14-day intervals (seven injections. The observed milk yield was compared with the yield expected by the extension model. An increase of 5.3% was observed in milk yield in response to the bST-r. This increase is lower than that reported in the literature in response to the growth hormone in dairy cattle. It is concluded that extension model used in the present work is reliable for extending the lactation curve in Holstein cows, and the increase in milk yield in response to the application of bST-r, determined in the same animal using the extension model, was lower than that reported by other authors.Um modelo de extensão de curvas de lactância foi utilizado para determinar o efeito da somatotropina bovina recombinante (bST-r sobre a produção de leite em vacas Holstein. Este modelo, que utiliza os valores ajustados obtidos pelo modelo de Wood, foi testato nos registros de 66 vacas. A produção de leite predita com o modelo de extensão e a produção observada foram comparadas e não se observaram diferenças significativas (P>0,05. Uma vez validado o modelo de extensão, utilizaram-se os controles de produção de leite (de cada 15 dias de 199 vacas. As vacas receberam injeções de 500mg de bST-r via subcutânea. As injeções fora aplicadas a partir dos 100 dias de lactação a intervalos de 14 dias (sete injeções. A produção de leite observada foi

Leptospirosis serosurvey in bovines from Brazilian Pantanal using IGG ELISA with recombinant protein LipL32 and microscopic agglutination test Sorodiagnóstico de leptospirose em bovinos do Pantanal brasileiro utilizando ELISA IgG com proteína recombinante LipL32 e soroaglutinação microscópica

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Renata Graça Pinto Tomich

2007-12-01

Full Text Available This investigation was carried out in Brazilian Pantanal: region with important biodiversity. This region's climatic conditions, hydrology and geomorphology as well as the existence of great variety of wild species favor the maintenance of the Leptospira in the environment. The aim of this study was to evaluate IgG ELISA with recombinant protein LipL32 in comparison with microscopic agglutination test (MAT and additionally contribute to the knowledge of the distribution of the one of most important worldwide zoonotic infection, assessing the seropositivity of bovine leptospirosis in beef cattle herds of Brazilian Pantanal, an important ecological preserved area, where cattle constitute not only the most important economic resource but also the major activity compatible of the conservation of natural resource of the region. Out of 282 samples of cattle serum analyzed, 143 (50.71% were positive in MAT. The serovar Hardjo (genotypic Hardjoprajitno and Hardjobovis, Wolffi and Ballum showed the largest frequency of reactive samples. In the IgG ELISA rLipL32, 161 samples (57.09% were positive. This result was higher than obtained by MAT (pEste estudo foi realizado no Pantanal brasileiro: região que apresenta importante biodiversidade. As condições de clima, hidrologia e geomorfologia dessa região, bem como a existência de grande variedade de espécies animais silvestres, favorecem a manutenção da Leptospira no meio ambiente. O objetivo desse estudo foi avaliar o ELISA IgG com proteína recombinante LipL32 em comparação com a soroaglutinação microscópica (SAM para o diagnóstico sorológico de Leptospira. Adicionalmente, contribuir para o conhecimento da distribuição da leptospirose bovina, uma das mais importantes zoonoses mundialmente distribuída. Foi avaliada a soropositividade para essa bactéria em rebanhos bovinos de corte da região do Pantanal, uma área onde o bovino constitui não apenas o recurso econômico mais importante

Nuevo método para medir un inductor de proteínas recombinantes

OpenAIRE

Fernández Castañé, Alfred

2012-01-01

El IPTG es un azúcar sintético análogo de la lactosa que se utiliza para la inducción de la producción de proteínas en la bacteria Escherichia coli. En la presente tesis doctoral se ha desarrollado por primera vez un método analítico para medir el IPTG en el medio de cultivo y dentro de las células que ha permitido estudiar el comportamiento de inducción en cultivos de alta densidad celular así como optimizar su dosis para obtener la máxima cantidad de producto.

Vacunas terapéuticas recombinantes contra el cáncer del cuello uterino

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BERUMEN JAIME

1997-01-01

Full Text Available Durante el desarrollo del cáncer cervicouterino se inducen mecanismos para evadir el sistema inmune, como son la disminución de la expresión de moléculas de antígeno mayor de histocompatibilidad I y la secreción de citocinas por las células tumorales. Como consecuencia de ello, la estimulación de linfocitos T citotóxicos (LTC y cooperadores (TC, de células asesinas naturales (AN y macrófagos es muy deficiente. Para inducir una respuesta inmune efectiva contra el tumor, se requiere la estimulación simultánea de múltiples componentes del sistema inmune: por vía sistémica la estimulación de LTC y TC contra epítopos del virus del papiloma humano, y en un nivel local, la inducción de la secreción de citocinas por el tumor, para aumentar el procesamiento y la presentación de blancos tumorales, así como la estimulación de los linfocitos, AN y macrófagos que infiltran el tumor.

EXPRESIÓN DE IDURONATO 2-SULFATO SULFATASA HUMANA RECOMBINANTE (IDShr EN Pichia pastoris

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Raúl Alberto Poutou

2005-06-01

Full Text Available El objetivo de este trabajo fue expresar la enzima humana iduronato 2-sulfato sulfatasa en la levadura metilotrófica Pichia pastoris. La deficiencia de esta enzima causa una enfermedad denominada Síndrome de Hunter. Siete clones fueron seleccionados por PCR (10, 28, 92, 94, 144, 149 y 153 al amplificar una banda de 826pb, indicativo de la presencia de la IDSh y de la orientación del fragmento. Diferentes medios de cultivo se emplearon en la fase de crecimiento (YPG, YPGli y BMGliY, la fase de inducción fue llevada a cabo cambiando el medio de crecimiento por BMMY. Una vez crecido en YPGli, los clones 10, 28, 144, 149 y 153 mostraron actividad IDS de 1.53, 2.95, 4.35, 4,07 y 4.15 nmol/h mg a las 24, 48, 72 y 120h de inducción respectivamente. El clon 28 produjo 4.21nmol/h mg al crecer en YPG; sólo los clones 92 y 94 produjeron mejores actividades cuando se crecieron en BMGliY; reportando 1.62 y 1.20nmol/mg h respectivamente. La producción de la IDShr se logró en fermentador de 1l, con medio salino (MBS-sF con el clon IDS28. El crecimiento se realizó en cultivo discontinuo utilizando glicerol (fuente de carbono y energía hasta obtener 12.08g/l de biomasa seca. Para el paso de inducción se utilizó un cultivo alimentado con metanol (<1% (v/v; este último sirvió como fuente de carbono y energía e indujo la expresión de IDShr actuando sobre el promotor nativo AOX1 presente en el constructo pPIC9- IDSh. La actividad específica osciló entre 25.4 y 29.36 nmol/mg h. Se destaca que el valor de referencia de nuestro laboratorio para la IDSh en plasma humano es 12.58 nmol/mg h.

Heavy impurity collection at the plasma edge of the stellarator W VII A

International Nuclear Information System (INIS)

Schou, J.

1981-12-01

The presence of impurities at the plasma edge of the Wendelstein VII-A stellarator was studied by means of carbon probes that were exposed to up to 200 plasma discharges in helium. The probes were subsequently analysed with 1 MeV 4 He + Rutherford Backscattering. The average impurity deposition for Ti, Mo and wall components (Fe, Cr, Ni) was 2-4 x 10 12 atoms/cm 2 , 6 x 10 10 atoms/cm 2 and 1 x 10 11 atoms/cm 2 per discharge, respectively. With the exception of Ti this impurity deposition is more than one order of magnitude smaller than the corresponding results from comparable tokamaks. (orig.)

Agenda 21 haridusprogramm / Imbi Henno

Index Scriptorium Estoniae

Henno, Imbi

2000-01-01

1992. a Rio de Janeiros toimunud ÜRO keskkonna- ja arengukonverentsil võeti vastu "Agenda 21", määrab kindlaks riikide säästva arengu alased põhisuunad käesoleval sajandil. 1997. a. Rio jätkukonverentsil tegi ÜRO Säästva Arengu Komisjon valitsustele ettekirjutuse - viia ellu "Agenda 21" põhimõtted. ÜRO Säästva Arengu Komisjoni eestvõtmisel võeti 1998. a. vastu ka "Agenda 21" 36. peatüki "Haridus, koolitus ja avalikkuse teadlikkus" laiendatud versioon, mille eesmärk on edendada riikidevahelist koostööd ja säästva arengu alast teadlikkust

Possible way to check up superbanana transport effects in present-day stellarators

International Nuclear Information System (INIS)

Bykov, V.E.; Volkov, E.D.; Georgievskij, A.V.; Shishkin, A.A.

1986-01-01

An important, as yet unanswered question in stellarator research is the following: how dangerous is the superbanana transport to the plasma confinement? Comparison of experimental data with theoretical transport coefficients indicates that the superbanana transport does occur in experiments. But it is believed that the experimental plasma loss rates (W-VIIA) are considerably lower than those predicted by neoclassical theory. The existing inconsistencies make it necessary to search for additional ways to find out whether the superbanana transport is feasible. One of possible ways is connected with the fact that the neoclassical superbanana transport coefficients depend essentially on the harmonic composition of the magnetic field

The research agenda for trauma critical care.

Science.gov (United States)

Asehnoune, Karim; Balogh, Zsolt; Citerio, Giuseppe; Cap, Andre; Billiar, Timothy; Stocchetti, Nino; Cohen, Mitchell J; Pelosi, Paolo; Curry, Nicola; Gaarder, Christine; Gruen, Russell; Holcomb, John; Hunt, Beverley J; Juffermans, Nicole P; Maegele, Mark; Midwinter, Mark; Moore, Frederick A; O'Dwyer, Michael; Pittet, Jean-François; Schöchl, Herbert; Schreiber, Martin; Spinella, Philip C; Stanworth, Simon; Winfield, Robert; Brohi, Karim

2017-09-01

In this research agenda on the acute and critical care management of trauma patients, we concentrate on the major factors leading to death, namely haemorrhage and traumatic brain injury (TBI). In haemostasis biology, the results of randomised controlled trials have led to the therapeutic focus moving away from the augmentation of coagulation factors (such as recombinant factor VIIa) and towards fibrinogen supplementation and administration of antifibrinolytics such as tranexamic acid. Novel diagnostic techniques need to be evaluated to determine whether an individualised precision approach is superior to current empirical practice. The timing and efficacy of platelet transfusions remain in question, while new blood products need to be developed and evaluated, including whole blood variants, lyophilised products and novel red cell storage modalities. The current cornerstones of TBI management are intracranial pressure control, maintenance of cerebral perfusion pressure and avoidance of secondary insults (such as hypotension, hypoxaemia, hyperglycaemia and pyrexia). Therapeutic hypothermia and decompressive craniectomy are controversial therapies. Further research into these strategies should focus on identifying which subgroups of patients may benefit from these interventions. Prediction of the long-term outcome early after TBI remains challenging. Early magnetic resonance imaging has recently been evaluated for predicting the long-term outcome in mild and severe TBI. Novel biomarkers may also help in outcome prediction and may predict chronic neurological symptoms. For trauma in general, rehabilitation is complex and multidimensional, and the optimal timing for commencement of rehabilitation needs investigation. We propose priority areas for clinical trials in the next 10 years.

Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

International Nuclear Information System (INIS)

Oesterud, B.; Rapaport, S.I.

Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

Terapia biológica en enfermedades reumatológicas

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Manuel F Ugarte-Gil

2013-04-01

Full Text Available El advenimiento del uso de terapias biológicas en Reumatología ha modificado significativamente el pronóstico de pacientes portadores de artritis reumatoide (AR, artritis juvenil (AJ, espondilitis anquilosante (EA, entre otras enfermedades. A diferencia de las terapias convencionales estos productos biológicos se dirigen a los llamados blancos terapéuticos ya sea estas una línea celular, un mediador inflamatorio o un receptor de superficie. Estos compuestos son producidos por células vivas mediante la tecnología del ADN recombinante. Estos compuestos pueden tener componentes humano y animal [quiméricos (Xi, humanizados (Zu], o completamente humanos (H lo cual se reconoce por las letras que se incluyen en el nombre de cada uno. En el campo de la Reumatología, el primer compuesto utilizado fue el etanercept (anti-factor de necrosis tumoral o anti-TNF aprobado en 1998, pero otros anti-TNF han demostrado su beneficio en AR, como en EA y AJ. Los inhibidores de Interleucina (IL-1 casi no se usan en AR actualmente, pero si los inhibidores de IL-6, así como los agentes contra las células B y los agonistas de CTLA-4 (Cytotoxic T lymphocyte antigen. Existe asimismo un compuesto dirigido al BLyS (B-lymphocyte stimulator el cual se usa en lupus eritematoso sistémico y otro dirigido al receptor activador del factor nuclear κB (RANKL, receptor activator of nuclear factor-κB ligand que se usa en osteoporosis. Con el avance en el conocimiento de la patogenia de las enfermedades reumαticas, se vienen reconociendo otra blancos terapιuticas. En los aρos venideros, este campo ha de expandirse en proporciones geomιtricas

Caracterização das fibras musculares do músculo Semitendinosus de bezerros mestiços Angus-Nelore recebendo somatotropina bovina recombinante (rbST até a desmama Characterization of Semitendinosus muscle fibers in pre-weaning Angus-Nellore crossbred calves receiving recombinant bovine somatotropin (rbST

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Rafael da Costa Cervieri

2005-06-01

Full Text Available Objetivando-se estudar o efeito da somatotropina bovina recombinante (rbST sobre a freqüência de distribuição e o diâmetro das fibras musculares do músculo Semitendinosus, 36 bezerros mestiços ½Angus-Nelore, com idade inicial de 63 ± 17 dias e pesando 76,8 ± 14,7 kg, criados em pastagem de Brachiaria decumbens e suplementados em creep feeding, foram submetidos a dois tratamentos até a desmama (217 dias: 18 bezerros receberam 1,4 mg/kg de rbST (Boostin® a cada 14 dias e 18 receberam solução salina (controle. As amostras de músculo foram coletadas aos 117 (biópsia e aos 217 dias de idade, quando foram abatidos cinco animais por tratamento. Os animais suplementados apresentaram maior diâmetro para as fibras do tipo glicolítica de contração rápida (FG aos 117 dias e tendência de aumento aos 217 dias e não diferiram em relação ao grupo controle quanto ao diâmetro das fibras oxidativas-glicolíticas de contração rápida (FOG e oxidativas de contração lenta (SO e à frequência de FG, FOG e SO aos 117 e 217 dias de idade. Independentemente da aplicação de rbST, houve significativo aumento do diâmetro das fibras SO e FOG, tendência de aumento de diâmetro das fibras FG, maior frequência de SO e redução da frequência de FG entre 117 e 217 dias de idade. A utilização de somatotropina exógena possibilitou maior hipertrofia das fibras musculares brancas de contração rápida em bezerros suplementados em creep feeding durante a fase de cria, sem interferir na frequência de distribuição dos tipos de fibras no músculo Semitendinosus.The objective of this experiment was to study the effect of the recombinant bovine somatotropin (rbST on the percentage distribution and diameter of semitendinosus muscle fibers. Thirty-six ½ Angus-Nellore crossbred bull calves, 63 ± 17 days old and weighting 76.8 ± 14.7 kg, raised in Brachiaria decumbens pastures and creep fed, were assigned to one of two treatments until weaning

Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

Science.gov (United States)

Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

2017-07-24

Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

Nuevos esquemas de inmunoterapia específicas con alérgenos

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José Fernando Cantillo

2010-09-01

Con estos nuevos esquemas se han diseñado vacunas basadas en alérgenos recombinantes y variantes o péptidos derivados de éstos, para ser administrados solos o con adyuvantes en preparaciones que favorecen la captación y presentación antigénica por las células dendríticas o tienen como blanco las células efectoras, como mastocitos y basófilos. Los estudios in vitro, en modelos animales y algunos en fase clínica en humanos, indican que estas preparaciones pueden brindar protección frente a la exposición alergénica o mejorar la sintomatología, al inducir la producción de anticuerpos bloqueadores de la actividad de la IgE, de células T reguladoras y de citocinas del perfil Th1.

Presentación de las V Jornadas del Instituto de Inmunología Clínica

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Guillermo Terán-Ángel

2013-12-01

Full Text Available La "V Jornada Científica del Instituto de Inmunología Clínica de la Universidad de los Andes" es un evento que se realiza en e l marco de la celebración de nuestro vigésimo aniversario de creación. En estas Jornadas se realizan actividades académicas de actualización (conferencias, presentación de trabajos libres, cursos y talleres prejornadas en el área de la inmunología y en general de las diferentes ramas de la biomedicina. Como eventos previos a las Jornadas se realizan dos cursos, el primero de clonación y producción de proteínas recombinantes seguido de un curso de inmunodiagnóstico . También se realiza un taller de manejo de infecciones recurrentes

Revisión sobre la problemática y los últimos avances en el control de la garrapata Boopilus microplus.

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César Mora Hernández

1998-10-01

Full Text Available La garrapata Boopilus microplus es el ectoparásito más importante de la ganadería bovina en los trópicos. A raíz de su proliferación, se convirtió en un importante problema económico y, el surgimiento de la producción animal intensiva, estimuló el desarrollo de investigaciones sobre la forma de controlar esta plaga. Estos estudios hicieron posible la creación de diversos métodos de control: la formulación de los nuevos radicales químicos, el control biológico, genético, inmunológico, y el empleo de técnicas de ingeniería genética para la síntesis de vacunas recombinantes, que se emplean con éxito en algunas explotaciones ganaderas de América Latina.

Eficácia e segurança da vacina brasileira contra hepatite B em recém-nascidos Eficiencia y seguridad de la vacuna brasilera contra hepatitis B en recién-nacidos Efficacy and safety of the Brazilian vaccine against Hepatitis B in newborns

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Expedito José de Albuquerque Luna

2009-12-01

Full Text Available OBJETIVO: Analisar a eficácia e segurança de vacina recombinante contra hepatite B em recém-nascidos. MÉTODOS: O estudo foi conduzido em hospital geral do município de Guarulhos, SP, entre 2002 e 2005. A vacina recombinante contra hepatite B do Instituto Butantan (VrHB-IB foi analisada em dois ensaios clínicos. Em ambos os ensaios, os recém-nascidos foram alocados aleatoriamente ao grupo experimental ou controle (vacina de referência. Os recém-nascidos receberam três doses das vacinas, uma em até 24 h após o nascimento e as subseqüentes 30 e 180 dias após. No primeiro ensaio 538 recém-nascidos completaram o protocolo e no segundo ensaio, 486. Considerou-se critério de equivalência a diferença na soroproteção inferior a 5%. RESULTADOS: A soroproteção no primeiro ensaio (anti HBs > 10mUI/ml foi de 92,5% (247/267 no grupo experimental, comparada a 98,5% (267/271 no grupo controle (p = 0,001. Com este resultado, a VrHB-IB não atingiu o critério de equivalência estabelecido. Após o aumento da concentração de antígeno na vacina para 25¼g, a soroproteção no segundo ensaio foi de 100% no grupo experimental e 99,2% no grupo controle. Nenhum evento adverso grave foi registrado. CONCLUSÕES: A vacina VrHB-IB modificada foi considerada equivalente à vacina de referência e seu uso recomendado à vacinação de recém-nascidos.OBJETIVO: Analizar la eficiencia y seguridad de vacuna recombinante contra hepatitis B en recién-nacidos. MÉTODOS: El estudio fue conducido en hospital general del municipio de Guarulhos, Sureste de Brasil, entre 2002 y 2005. La vacuna recombinante contra hepatitis B del Instituto Butantan (VrHB-IB fue analizada en dos ensayos clínicos. En ambos ensayos, los recién-nacidos fueron distribuidos aleatoriamente en el grupo experimental o control (vacuna de referencia. Los recién-nacidos recibieron tres dosis de las vacunas, una en máximo 24 h posterior al nacimiento y las subsecuentes 30 y 180 d

IPP: Annual report 1982

International Nuclear Information System (INIS)

1982-01-01

This report presents a detailed outline of the work accomplished within the framework of the Tokamak projects ASDEX and ASDEX Upgrade and the JET and NET projects, the stellarator projects VIII-A, VII-AS and VII-X, and of stellarator reactor system studies. The various scientific research departments, such as Experimental Plasma Physics 1, 2 and 3, Theoretical Plasma Physics 1 and 2, Plasma-Wall. Interactions, and Information Sciences give an account of the results of their research and development work. Further reports on the 1982 activities deal with a) the organisational structure of the IPP, b) administrative and business items, c) scientific publications and conference proceedings, and with d) IPP-supported projects at universities. (GG) [de

Plataformas de expresión en plantas de péptidos humanos terapéuticos: expresión transitoria y estable

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Arnaldo Noguera

2013-08-01

Full Text Available Las plantas representan un sistema de expresión alternativo para la producción de proteínas heterólogas complejas tales como vacunas, antígenos, anticuerpos, eritroproyetina e insulina humana. Este sistema posee diversas ventajas sobre los sistemas de expresión tradicional basados en el cultivo de células de bacterias, levaduras, insectos y mamíferos, como su bajo costo de producción, menor tiempo para alcanzar la producción a gran escala, expresión, modificación y ensamblaje apropiado de la proteína recombinante y ausencia de riesgo de contaminación con patógenos humanos. En la última década la ingeniería genética de plantas ha utilizado ampliamente los sistemas de expresión estable basados en la bacteria Agrobacterium tumefaciens y la expresión transitoria basada en los vectores virales de plantas para la obtención de compuestos beneficiosos para la salud y el bienestar del hombre. La introducción de estos elementos virales en los sistemas de producción de proteínas recombinantes ha simplificado la manipulación y el proceso de infección de las plantas con el gen quimérico. Aunado a esto, el entendimiento de la inmunogenicidad que poseen los glicanos de origen vegetal sobre la actividad de los péptidos heterólogos, ha permitido dilucidar cuales son las vías moleculares más convenientes para expresar, ensamblar, compartamentalizar e incrementar la acumulación de las proteínas de interés. Con la presente revisión se busca proporcionar al lector una información detallada acerca de las estrategias de expresión heterólogas que utilizan sistemas vegetales, los principales agentes terapéuticos desarrollados basados en estos sistemas y la importancia biológica de las modificaciones post–traduccionales de los péptidos recombinantes. In plant expression platforms of therapeutic human peptides: transient and stable expression Abstract Plants represent an alternative expression system for the production of

Review: Pichia pastoris represents an alternative for human glycoprotein production for therapeutic use. Fermentation strategies Revisión de tema: Pichia pastoris, una alternativa para la producción de glicoproteínas humanas de uso terapéutico. Estrategias de fermentación

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Barrera Avellaneda Luis Alejandro

2003-12-01

Full Text Available Producing human proteins in lower organisms' cells using recombinant technology represents a very promising approach for treating many diseases produced by a particular protein deficiency, including close to 40 lysosomal storage diseases. Although E. coli has been the first host successfully employed in expressing human recombinant proteins, it has some limitations owing to its inability to perform some post-traductional steps such as glycosylation. The yeast Saccharomyces cerevisiae (S. cerevisiae has thusbeen initially considered and used. However, S. cerevisiae glycosylates proteins in a very different way to human cells producing highly antigenic proteins and thus some other non-conventional yeasts such as Pichia pastoris have been used recently. Human protein expression is not assodated with growth in this system; growth may occur at high cell concentrations, increasing heterologous protein productivity and yield. The system employs a very efficient, methanol-induced promoter which may be used as sole carbon and energy source. Post-traductional modifications seem more similar to human cells than those produced by other non-mammalian systems used in producing human glycoproteins; they do not secrete large amounts of endogenous proteins, simplifying expressed protein purification. This review presents some strategies for producing heterologous proteins in high density cultures using P. pastoris as an expression system.La producción de proteínas humanas en células de organismos inferiores, mediante tecnología recombinante es una muy prometedora aproximación al tratamiento de muchas enfermedades producidas por la deficiencia de una proteína en particular, entre ellas cerca de 40 enfermedades de almacenamiento lisosomal. Aunque Escherichia coli (E. coli fue el primer hospedero empleado con éxito para expresar proteínas humanas recombinantes, tiene algunas limitaciones, causadas principalmente por su inhabilidad para hacer algunas

Toxoplasma gondii: humoral and cellular immune response of BALB/c mice immunized via intranasal route with rTgROP2 Toxoplasma gondii: avaliação da resposta imune humoral e celular de camundongos BALB/c imunizados pela via nasal com rTgROP2

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Michelle Igarashi

2010-12-01

Full Text Available TgROP2 is an intracellular protein associated with rhoptries of Toxoplama gondii and an antigen component of a candidate vaccine for toxoplasmosis. The purpose of the present study was to evaluate the efficacy of rTgROP2 to stimulate humoral and cellular immune responses in BALB/c mice via intranasal injection. TgROP2 partial coding sequence was (196-561 amplified by PCR from genomic T. gondii RH strain DNA and cloned into the pTrcHis expression vector. Escherichia coli Rosetta 2 cells transformed with pTrcHis-TgROP2 showed high levels (~1 mg.mL-1 of recombinant protein after 4 hours of IPTG induction. Recombinant TgROP2 exhibited an apparent Mr equal to 54 kDa. In order to test immunogenicity of the recombinant protein, 10 BALB/c mice received 10 µg of rROP2 protein + 10 µg of Quil-A via intranasal injection. Doses were administered at days 0, 21, and 42. Three animals were euthanized and used to evaluate cell-ular immune response on day 62. Five (50% and two (20% out of ten animals produced IgG (DO mean = 0.307; cut-off = 0.240 and IgA (DO mean = 0.133, cut-off = 0.101, respectively, by ELISA on day 62. The proliferation of splenocytes revealed high stimulation index (SI when co-cultured with 5, 10 and 15 µg.mL-1 of rTgROP2. These results indicate that intranasal immunization with recombinant protein ROP2 plus Quil-A can elicit both cellular and humoral immune responses in BALB/c mice.TgROP2 é uma proteína localizada nas roptrias do Toxoplasma gondii, sendo um antígeno candidato a componente de uma vacina contra a toxoplasmose. O objetivo do presente estudo foi avaliar a eficácia da TgROP2 recombinante em estimular a resposta imune celular e humoral de camundongos BALB/c após estímulo intranasal. A sequência da TgROP2 foi amplificada pela PCR a partir da cepa RH e clonada em vetor de expressão pTrc-His. Após a transformação em Escherichia coli- Rosetta 2, a pTrcHis-TgROP2 exibiu alto nível de expressão após 4 horas de indu

Desenvolvimento de vacina recombinante de proteína M de Streptococcus equi subsp. equi

OpenAIRE

MACIEL, Liana Flores

2012-01-01

A equinocultura no Brasil ganha espaço em setores ligados ao lazer, cultura e turismo, sendo responsável por milhões de empregos. A Adenite Equina causada pelo Streptococcus equi subsp. equi é uma doença do aparelho respiratório de elevado impacto econômico, gerando gastos com mão-de-obra e perda de desempenho dos animais. Para amenizar este problema, medidas profiláticas são importantes, como por exemplo, a vacinação. Porém, as vacinas disponíveis no mercado protegem apenas 50% dos animai...

Erythropoïétine recombinante, traitement de l'anémie grave d'un ...

African Journals Online (AJOL)

Un nourrisson de 25 mois présentant un paludisme grave forme anémique décompensé avec un taux d'hémoglobine de 1,9 g/dl dont les parents sont des Témoins de Jéhovah a été traité par de l'EPOr en lieu et place d'une transfusion sanguine. En effet, les parents étaient contre la transfusion sanguine en raison de leur ...

Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue

OpenAIRE

Liliana Morales; Myriam L. Velandia; María Angélica Calderon; Jaime E. Castellanos; Jacqueline Chaparro-Olaya

2017-01-01

Introducción. El dengue es una enfermedad causada por uno de los cuatro serotipos del virus del dengue (DENV) y es endémica en, aproximadamente, 130 países. Su incidencia ha aumentado notablemente en las últimas décadas, así como la frecuencia y la magnitud de los brotes. A pesar de los esfuerzos, no existen tratamientos profilácticos ni terapéuticos contra la enfermedad y, en ese contexto, el estudio de los procesos que gobiernan el ciclo de infección del DENV es esencial para desarrollar...

Equid herpesvirus type 1 activates platelets.

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Tracy Stokol

Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

ASPECTOS ÉTICOS DEL ENTENDIMIENTO PÚBLICO DE LA BIOTECNOLOGÍA ASPECTOS ÉTICOS DO ENTENDIMENTO PÚBLICO DA BIOTECNOLOGIA ETHICAL POINTS OF VIEW OF BIOTECHNOLOGY’S PUBLIC PERCEPTION

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Bernardo Elias Correa Soares

2003-01-01

Full Text Available La práctica del control social de la biotecnología demanda salidas bases de naturaleza ética a fin de racionalizar la aplicación de los principios científicos y permitir beneficios para la sociedad en general. Mientras el uso de la tecnología recombinante en productos médicos y farmacéuticos tiene gran aceptación por parte de la sociedad, gracias a la evidente mejora causada por la cura de enfermedades, no está tan claro para el consumidor el valor real de la investigación genética para mejorar la calidad de los alimentos. Es grande la demanda por más información científica para el público a efectos de movilizar la sociedad hacia esclarecimientos en el pensamiento biotecnológicoA prática do controle social da biotecnologia exige sólidas bases de natureza ética a fim de racionalizar a aplicação dos princípios científicos e permitir benefícios para a sociedade em geral. Enquanto que o uso da tecnologia recombinante nos produtos médicos e farmacêuticos tem grande aceitação por parte da sociedade, graças a evidente melhora causada pela cura de enfermidades, não está tão claro para o consumidor o valor real da pesquisa genética para melhorar a qualidade dos alimentos. A demanda por mais informação científica para o público, é enorme, com a conseqüência de mobilizar a sociedade para esclarecimentos no pensamento biotecnológicoThe practice of biotechnological social control demands ethical bases in order to rationalize the application of scientific principles and for allowing benefits to society. While the use of recombinant technology in pharmaceutical and medical products has great acceptance by society, as consequence of the evident improvement caused by the cure of diseases, the consumer hasn’t a clear idea of the real value of genetic research to improve food quality. There is a great demand for more scientific information by the public with the purpose of mobilizing society toward clarifications in the

Clonagem e expressão da glicoproteína transmembrana do retrovírus HTLV-1 em células de mamíferos Cloning and transmembrane glycoprotein expression of the retrovirus HTLV-1 in mammals' cells

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Flora Cristina Lobo Penteado

2006-04-01

Full Text Available O retrovírus linfotrópico de células T humanas tipo 1 é o agente etiológico da leucemia das células T do adulto e da paraparesia espástica tropical/mielopatia associada ao HTLV-1. O genoma proviral é composto por 9.032 pares de bases, contendo genes estruturais e regulatórios. A glicoproteína transmembrana gp 21 é codificada pelo gene estrutural env. O desenvolvimento de metodologias para a expressão heteróloga de proteínas, assim como a obtenção de uma linhagem celular que expresse a gp 21 recombinante constitutivamente são os principais objetivos do trabalho. O fragmento codificante da gp 21 foi amplificado por Nested-PCR e clonado no vetor pCR2.1-TOPO. Posteriormente, foi realizada a subclonagem no vetor de expressão pcDNA3.1+. A transfecção da linhagem celular de mamíferos HEK 293 foi realizada de maneira transitória e permanente. A produção da gp 21 recombinante foi confirmada por citometria de fluxo e a linhagem celular produtora será utilizada em ensaios de imunogenicidade.The retrovirus HTLV-1 is the etiological agent of the adult T-cell leukemia and HTLV-1 associated myelopathy/tropical spastic paraparesis. The proviral genome has 9,032 base pairs, showing regulatory and structural genes. The env gene encodes for the transmembrane glycoprotein gp 21. The development of methodologies for heterologous protein expression, as well as the acquisition of a cellular line that constituently expresses the recombinant, were the main goals of this work. The DNA fragment that encodes for gp 21 was amplified by nested-PCR and cloned into a pCR2.1-TOPO vector. After which, a sub-cloning was realized using the expressing vector pcDNA3.1+. The transfection of mammalian cells HEK 293 was performed transitorily and permanently. Production of the recombinant gp 21 was confirmed by flux cytometry experiments and the cell line producing protein will be used in immunogenicity assays.

Construcción de un banco de clones de cDNA a partir de mRNA de P. falciparum

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María Orfa de Rojas

1988-06-01

Full Text Available Se aisló mRNA-poli A de parásitos de P. falciparum (cepa Colombiana FCB-2 con una edad entre 34-36 horas. Esta fracción de mRNA fue traducida in-vitro utilizando un lisado de reticulocitos de conejo suplementado en algunos casos con tRNA del parásito o tRNA de levadura. Los productos de la traducción in-vitro aparecen en un rango entre 20 y 200 kd mostrando una gran similitud con las proteínas sintetizadas in-vitro en cultivos altamente sincronizados del parásito. A partir de mRNA-poli A caracterizado en ésta forma se construyó una genoteca de cDNA en el fago A gtl0. La eficiencia de clonación fue de 4.4 x 106 recombinantes por microgramo de cDNA.

Factors and factorizations of graphs proof techniques in factor theory

CERN Document Server

Akiyama, Jin

2011-01-01

This book chronicles the development of graph factors and factorizations. It pursues a comprehensive approach, addressing most of the important results from hundreds of findings over the last century. One of the main themes is the observation that many theorems can be proved using only a few standard proof techniques. This stands in marked contrast to the seemingly countless, complex proof techniques offered by the extant body of papers and books. In addition to covering the history and development of this area, the book offers conjectures and discusses open problems. It also includes numerous explanatory figures that enable readers to progressively and intuitively understand the most important notions and proofs in the area of factors and factorization.

Proteínas del gluten y reología de trigos harineros mexicanos influeciados por factores ambientales y genotípicos Gluten proteins and rheology of Mexican bread wheats as affected by environmental and genotypic factors

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Micaela De la O Olán

2010-09-01

Full Text Available El objetivo de este estudio fue conocer el efecto de factores ambientales y genotípicos sobre los parámetros de calidad industrial y sobre la cantidad y relación de proteínas monoméricas y poliméricas del gluten en 24 líneas recombinantes de trigos harineros de temporal. El cultivo se desarrolló en cinco condiciones ambientales generadas por manejo agronómico, ciclo otoño-invierno 2006/2007, en Roque, Guanajuato, México. Se evaluaron el tiempo de amasado (TMA, fuerza (ALVW, extensibilidad (ALVPL de la masa, fracción rica en gliadina (50PS y en glutenina (50PI, y su relación (50PS/50PI. Las mejores combinaciones de gluteninas de alto y bajo peso molecular para TMA y ALVW fueron los genotipos con 1, 17+18, 5+10/Glu-A3c, Glu-B3g, Glu-D3b; 1, 17+18, 5+10/Glu-A3c, Glu-B3h, Glu-D3b, y 2*, 17+18, 5+10/Glu-A3c, Glu-B3g, Glu-D3b; para ALVPL, 2*, 17+18, 2+12/Glu-A3e, Glu-B3h, Glu-D3b; para 50PS, 2*, 17+18, 2+12/Glu-A3e, Glu-B3h, Glu-D3b; y 1, 17+18, 5+10/Glu-A3e, Glu-B3h, Glu-D3b. La relación 50PS/50PI fue mayor en genotipos con 2*, 17+18, 2+12/Glu-A3e, Glu-B3g, Glu-D3b. El TMA es mayor cuando aumenta la temperatura y la mejor ALVPL se obtiene en el ambiente bajo condiciones normales. La fracción 50PS y la relación 50PS/50PI son mayores cuando se realiza la fertilización con azufre, y se obtiene incremento de 50PI con riego limitado y aumento de temperaturas durante el llenado de grano.The objective of this study was to determine the effect of environmental and genotypic factors on industrial quality and on the monomeric and polymeric protein contents and ratio of 24 rainfed bread wheat recombinant lines. The cultivation was done in five environmental conditions generated by agronomic management in the autumn-winter 2006/2007 cycle, at Roque, Guanajuato, Mexico. The mixing time (TMA, strength (ALVW and extensibility (ALVPL of the dough, gliadin (50PS and glutenin (50PI rich fractions, and their ratio (50PS/50PI, were evaluated. The best

Presidendi külalised võib Tartusse ballile viia rong / Ingvar Bärenklau

Index Scriptorium Estoniae

Bärenklau, Ingvar, 1967-

2006-01-01

Ilmunud ka: Postimees : na russkom jazõke 21. nov. 2006, lk. 2. President Toomas Hendrik Ilvese ettepanekust korraldada presidendi iseseisvuspäeva vastuvõtt Tartus. Külaliste Tallinnast Tartusse sõidutamiseks tellitaks erirong Edelaraudteelt

FERM proteins in animal morphogenesis.

Science.gov (United States)

Tepass, Ulrich

2009-08-01

Proteins containing a FERM domain are ubiquitous components of the cytocortex of animal cells where they are engaged in structural, transport, and signaling functions. Recent years have seen a wealth of genetic studies in model organisms that explore FERM protein function in development and tissue organization. In addition, mutations in several FERM protein-encoding genes have been associated with human diseases. This review will provide a brief overview of the FERM domain structure and the FERM protein superfamily and then discuss recent advances in our understanding of the mechanism of function and developmental requirement of several FERM proteins including Moesin, Myosin-VIIA, Myosin-XV, Coracle/Band4.1 as well as Yurt and its vertebrate homologs Mosaic Eyes and EPB41L5/YMO1/Limulus.

Ebola viral disease: a review literature

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Saeed Reza Jamali Moghadam

2015-04-01

Full Text Available Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately 95% of the patients appear signs within 21 d after exposure. Typical features include fever, profound weakness, diarrhea, abdominal pain, cramping, nausea and vomiting for 3-5 days and maybe persisting for up to a week. Laboratory complications including elevated aminotransferase levels, marked lymphocytopenia, and thrombocytopenia may have occurred. Hemorrhagic fever occurs in less than half of patients and it takes place most commonly in the gastrointestinal tract. The symptoms progress over the time and patients suffer from dehydration, stupor, confusion, hypotension, multi-organ failure, leading to fulminant shock and eventually death. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer (four-fold contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. Passive transfer of serum collected from survivors of Junin virus or Lassa virus, equine IgG product from horses hypervaccinated with Ebola virus, a “cocktail” of humanized-mouse antibodies (ZMapp, recombinant inhibitor of factor VIIa/tissue factor, activated protein C, RNA-polymerase inhibitors and small interfering RNA nano particles are among the therapies in development. Preclinical evaluation is also underway for various vaccine candidates. One is a chimpanzee adenovirus vector vaccine; other vaccines involve replication-defective adenovirus serotype 5 and recombinant vesicular stomatitis virus.

Genital immunization of heifers with a glycoprotein Edeleted, recombinant bovine herpesvirus 1 strain confers protection upon challenge with a virulent isolate Imunização genital de bezerras com uma cepa recombinante do herpesvírus bovino tipo 1 defectiva na glicoproteína E confere proteção frente a desafio com um isolado virulento

Directory of Open Access Journals (Sweden)

Marcelo Weiss

2010-01-01

mild and transient vulvovaginitis (3/4 or mild to moderate genital lesions (1/4. In the IV group, the clinical signs lasted 4 to 8 days (x: 5.5 days. Clinical examination of the animals after challenge revealed that vaccination by both routes conferred some degree of protection, yet IV vaccination was clearly more effective in reducing the severity and duration of clinical disease. Furthermore, IV vaccination reduced the period of virus shedding in comparison with both groups. Taken together, these results demonstrate that SV265gE- is sufficiently attenuated upon IV vaccination in a low-titer dosis, is not readily reactivated after corticosteroid treatment and lastly, and more importantly, confers local protection upon challenge with a high titer of a virulent heterologous BoHV-1 isolate. Therefore, the use of this recombinant for genital immunization may be considered for prevention of BoHV-1-associated genital disease in the field.A infecção genital de novilhas ou vacas soronegativas pelo herpesvírus bovino tipo 1.2 (BoHV-1.2 pode resultar em vulvovaginite e infertilidade temporária. As vacinas atenuadas ou inativadas administradas pela via parenteral freqüentemente conferem proteção incompleta frente a desafio pela via genital. Este estudo relata uma avaliação da resposta imunológica e proteção conferida pela vacinação genital de bezerras soronegativas com uma cepa recombinante do BoHV-1 defectiva na glicoproteína E (SV265gE-. Um grupo de seis bezerras foi vacinado com a cepa SV265gE(0,2mL contendo 10(6,9TCID50 na submucosa da vulva (grupo IV; quatro bezerras foram vacinadas pela via intramuscular (IM; dose 10(7,6TCID50 e quatro bezerras permaneceram como controles não-vacinadas. As bezerras vacinadas pela via IV apresentaram edema e hiperemia leve e transitório na vulva e excretaram vírus em títulos baixos por alguns dias após a vacinação, porém uma bezerra soronegativa mantida em contato não soroconverteu. Administração de dexametasona

Factor XII (Hageman factor) deficiency

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/000545.htm Factor XII (Hageman factor) deficiency To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

Development of a lectin binding assay to differentiate between recombinant and endogenous proteins in pharmacokinetic studies of protein-biopharmaceuticals.

Science.gov (United States)

Weber, Alfred; Minibeck, Eva; Scheiflinger, Friedrich; Turecek, Peter L

2015-04-10

Human glycoproteins, expressed in hamster cell lines, show similar glycosylation patterns to naturally occurring human molecules except for a minute difference in the linkage of terminal sialic acid: both cell types lack α2,6-galactosyl-sialyltransferase, abundantly expressed in human hepatocytes and responsible for the α2,6-sialylation of circulating glycoproteins. This minute difference, which is currently not known to have any physiological relevance, was the basis for the selective measurement of recombinant glycoproteins in the presence of their endogenous counterparts. The assay is based on using the lectin Sambucus nigra agglutinin (SNA), selectively binding to α2,6-sialylated N-glycans. Using von Willebrand factor (VWF), factor IX (FIX), and factor VIIa (FVIIa), it was demonstrated that (i) the plasma-derived proteins, but not the corresponding recombinant proteins, specifically bind to SNA and (ii) this binding can be used to deplete the plasma-derived proteins. The feasibility of this approach was confirmed in spike-recovery studies for all three recombinant coagulation proteins in human plasma and for recombinant VWF (rVWF) in macaque plasma. Analysis of plasma samples from macaques after administration of recombinant and a plasma-derived VWF demonstrated the suitability and robustness of this approach. Data showed that rVWF could be selectively measured without changing the ELISAs and furthermore revealed the limitations of baseline adjustment using a single measurement of the predose concentration only. The SNA gel-based depletion procedure can easily be integrated in existing procedures as a specific sample pre-treatment step. While ELISA-based methods were used to measure the recombinant coagulation proteins in the supernatants obtained by depletion, this procedure is applicable for all biochemical analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

Costs and utilization of hemophilia A and B patients with and without inhibitors.

Science.gov (United States)

Armstrong, Edward P; Malone, Daniel C; Krishnan, Sangeeta; Wessler, Maj Jacob

2014-11-01

To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years. This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor. There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors. The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.

LIPASES PRODUZIDAS POR LEVEDURAS: CATALISADORES PODEROSOS PARA APLICAÇÕES INDUSTRIAIS

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Luiza Lux Lock

2007-12-01

Full Text Available O termo “enzimas lipolíticas” refere-se a lípases e hidrolases éster carboxílico. A produção de lipase é ampla entre as leveduras, mas poucas são capazes de produzir lipases com características interessantes e em quantidades suficientes para serem industrialmente úteis. A literatura relativa a lipases produzidas por Candida rugosa, Yarrowia (Candida lipolytica, Candida antarctica e outras leveduras produtoras de lípases é revisada. O uso de lípases recombinantes é discutido, com ênfase na utilização de sistemas de expressão heteróloga e desenho de quimeras. Finalmente, as três abordagens que visam à melhora da produção de lipase ou a modificação da seletividade do substrato da enzima (engenharia do meio, do biocatalisador e da proteína são discutidos.

Factors affecting construction performance: exploratory factor analysis

Science.gov (United States)

Soewin, E.; Chinda, T.

2018-04-01

The present work attempts to develop a multidimensional performance evaluation framework for a construction company by considering all relevant measures of performance. Based on the previous studies, this study hypothesizes nine key factors, with a total of 57 associated items. The hypothesized factors, with their associated items, are then used to develop questionnaire survey to gather data. The exploratory factor analysis (EFA) was applied to the collected data which gave rise 10 factors with 57 items affecting construction performance. The findings further reveal that the items constituting ten key performance factors (KPIs) namely; 1) Time, 2) Cost, 3) Quality, 4) Safety & Health, 5) Internal Stakeholder, 6) External Stakeholder, 7) Client Satisfaction, 8) Financial Performance, 9) Environment, and 10) Information, Technology & Innovation. The analysis helps to develop multi-dimensional performance evaluation framework for an effective measurement of the construction performance. The 10 key performance factors can be broadly categorized into economic aspect, social aspect, environmental aspect, and technology aspects. It is important to understand a multi-dimension performance evaluation framework by including all key factors affecting the construction performance of a company, so that the management level can effectively plan to implement an effective performance development plan to match with the mission and vision of the company.

Bioengineering of rFVIIa Biopharmaceutical and Structure Characterization for Biosimilarity Assessment

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Othman Montacir

2018-01-01

Full Text Available Eptacog alfa (NovoSeven® is a vitamin K-dependent recombinant Factor VIIa produced by genetic engineering from baby hamster kidney (BHK cells as a single peptide chain of 406 residues. After activation, it consists of a light chain (LC of 152 amino and a heavy chain (HC of 254 amino acids. Recombinant FVIIa undergoes many post-translational modifications (PTMs. The first ten glutamic acids of the N-terminal moiety are γ-carboxylated, Asn145 and Asn322 are N-glycosylated, and Ser52 and Ser60 are O-glycosylated. A head-to-head biosimilarity study was conducted for the originator and the first biosimilar AryoSeven™ to evaluate comparable bioengineering. Physicochemical properties were analyzed based on mass spectrometry, including intact mass, PTMs and higher-order structure. Both biotherapeutics exhibit a batch-to-batch variability in their N-glycan profiles. N-Glycopeptide analysis with UHPLC-QTOF-MSE confirmed N-glycosylation sites as well as two different O-glycopeptide sites. Ser60 was found to be O-fucosylated and Ser52 had O-glucose or O-glucose-(xylose1,2 motifs as glycan variants. Ion mobility spectrometry (TWIMS and NMR spectroscopy data affirm close similarity of the higher-order structure of both biologicals. Potency of the biodrugs was analyzed by a coagulation assay demonstrating comparable bioactivity. Consequently, careful process optimization led to a stable production process of the biopharmaceuticals.

Perioperative coagulation management and blood conservation in cardiac surgery: a Canadian Survey.

Science.gov (United States)

Taneja, Ravi; Fernandes, Philip; Marwaha, Gulshan; Cheng, Davy; Bainbridge, Daniel

2008-10-01

To determine which strategies are currently used for (anti)coagulation management and blood conservation during cardiac surgery in Canada. Institutional survey. University hospital. All sites performing cardiac surgery in Canada. None. The response rate was 85%. Anticoagulation with heparin is monitored routinely through the activated coagulation time (ACT). Less than 10% of centers use heparin concentrations (Hepcon HMS, Medtronic), thromboelastography, or other point-of-care tests perioperatively. Eighty percent of centers routinely use tranexamic acid as the primary antifibrinolytic agent; however aprotinin until recently, was used more commonly for patients at increased risk for bleeding. Retrograde autologous prime is commonly used (62%); however, cell savers are uncommon for routine patients undergoing cardiac surgery (29%). Although most hospitals use a hematocrit of 20% to 21% for transfusing red blood cells, more than 50% of intensive care units do not have written guidelines for the administration of protamine, fresh frozen plasma, platelets, or factor VIIa. At least one third of centers do not audit their transfusion practices regularly. The majority of Canadian institutions do not use point-of-care tests other than ACT. Most institutions do not have algorithms for management of bleeding following cardiac surgery and at least 30% do not monitor their transfusion practice perioperatively. Cardiac surgery patients in Canada may benefit from a standardized approach to blood conservation in the perioperative period.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) with chronic cough and preserved muscle stretch reflexes: evidence for selective sparing of afferent Ia fibres.

Science.gov (United States)

Infante, Jon; García, Antonio; Serrano-Cárdenas, Karla M; González-Aguado, Rocío; Gazulla, José; de Lucas, Enrique M; Berciano, José

2018-04-25

The aim of this study was to describe five patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) with chronic cough and preserved limb muscle stretch reflexes. All five patients were in the seventh decade of age, their gait imbalance having been initiated in the fifth decade. In four patients cough antedated gait imbalance between 15 and 29 years; cough was spasmodic and triggered by variable factors. Established clinical picture included severe hypopallesthesia predominating in the lower limbs with postural imbalance, and variable degree of cerebellar axial and appendicular ataxia, dysarthria and horizontal gaze-evoked nystagmus. Upper- and lower-limb tendon jerks were preserved, whereas jaw jerk was absent. Vestibular function testing showed bilateral impairment of the vestibulo-ocular reflex. Nerve conduction studies demonstrated normal motor conduction parameters and absence or severe attenuation of sensory nerve action potentials. Somatosensory evoked potentials were absent or severely attenuated. Biceps and femoral T-reflex recordings were normal, while masseter reflex was absent or attenuated. Sympathetic skin responses were normal. Cranial MRI showed vermian and hemispheric cerebellar atrophy predominating in lobules VI, VII and VIIa. We conclude that spasmodic cough may be an integral part of the clinical picture in CANVAS, antedating the appearance of imbalance in several decades and that sparing of muscle spindle afferents (Ia fibres) is probably the pathophysiological basis of normoreflexia.

Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

Science.gov (United States)

Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

2017-07-01

Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Activation of human factor V by factor Xa and thrombin

International Nuclear Information System (INIS)

Monkovic, D.D.; Tracy, P.B.

1990-01-01

The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polycarylamide gel electrophoresis followed by either autoradiography of 125 I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of M r 220,000 and 105,000. Although thrombin cleaved the M r 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the M r 220,000 peptide. The factor Xa dependent functional assessment of 125 I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the M r 220,000 peptide. The data indicate that factor Xa is as efficient an enzyme toward factor V as thrombin

The molecular genetics of Usher syndrome.

Science.gov (United States)

Ahmed, Z M; Riazuddin, S; Riazuddin, S; Wilcox, E R

2003-06-01

Association of sensorineural deafness and progressive retinitis pigmentosa with and without a vestibular abnormality is the hallmark of Usher syndrome and involves at least 12 loci among three different clinical subtypes. Genes identified for the more commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts from all these genes are found in many tissues/cell types other than the inner ear and retina, but all are uniquely critical for retinal and cochlear cell function. Many of these protein products have been demonstrated to have direct interactions with each other and perform an essential role in stereocilia homeostasis.

Factorization and non-factorization in diffractive hard scattering

International Nuclear Information System (INIS)

Berera, Arjun

1997-01-01

Factorization, in the sense defined for inclusive hard scattering, is discussed for diffractive hard scattering. A factorization theorem similar to its inclusive counterpart is presented for diffractive DIS. For hadron-hadron diffractive hard scattering, in contrast to its inclusive counterpart, the expected breakdown of factorization is discussed. Cross section estimates are given from a simple field theory model for non-factorizing double-pomeron-exchange (DPE) dijet production with and without account for Sudakov suppression

Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

Energy Technology Data Exchange (ETDEWEB)

Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

2008-06-03

Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

Energy Technology Data Exchange (ETDEWEB)

Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

2008-01-01

Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

Asjatundja soovitab Eesti Energia kiiresti börsile viia / Tiit Nigul ; interv. Andrus Karnau

Index Scriptorium Estoniae

Nigul, Tiit

2008-01-01

Eesti Energia endine juhatuse liige vastab küsimustele, mis puudutavad riigi energiapoliitikat ja -varustust, elektrienergia hinnatõusu, energiafirma börsileminekut, tasakaalu konkurentsiameti ja Eesti Energia vahel, ettevõtte tulusid, Narva Elektrijaamade tootmisvõimsust, koostööd Leedu tuumajaama projektiga, elektriturgu, ettevõtja Urmas Sõõrumaa süüdistamist siseinfo kasutamises, Eesti Energia strateegilist eesmärki saavutada aastaks 2015 kaks miljonit klienti

Euroopa päevik aitab tunde läbi viia / Epp Adler, Indrek Riigor

Index Scriptorium Estoniae

Adler, Epp

2008-01-01

Jaanuari lõpuni saavad kõik Eesti koolid tellida tasuta Euroopa päevikut, kus lisaks kalendrile on 96 lehekülge tekste tarbimise, ühiskonna ja Euroopa teemadel. Tallinna Nõmme Gümnaasiumi ajaloo, ühiskonnaõpetuse ja filosoofia õpetaja Indrek Riigor on päevikut kolm aastat tundides kasutanud

Desarrollo de una vacuna profiláctica de segunda generación contra el papilomavirus humano Development of a second generation prophylactic vaccine against human papillomavirus

Directory of Open Access Journals (Sweden)

Alonso Leonardo

2011-06-01

Full Text Available Los papilomavirus humanos (HPV son el agente etiológico del cáncer cervical (CC, la segunda causa de muerte por cáncer en mujeres. Se estima que medio millón de nuevos cánceres se diagnostica cada año, ocurriendo la mayoría de ellos en países en vías de desarrollo debido a la ausencia o ineficiencia de los programas masivos de detección temprana. Recientemente se han introducido en el mercado dos vacunas profilácticas contra las principales cepas oncogénicas de HPV, la cepa 16 y 18, responsables por el 80% de todos los CC. Estas vacunas se obtienen en forma recombinante y han demostrado ser extremadamente seguras y eficaces. Sin embargo, su impacto inmediato en la incidencia de la infección por HPV en países en vías de desarrollo será mínimo, debido principalmente al alto costo de las mismas. Existe la necesidad de contar con vacunas de segunda generación, de bajo costo y de aplicación masiva que permitan disminuir sensiblemente el número de CC en la población. Con este objetivo hemos desarrollado una plataforma de expresión recombinante que permite obtener partículas tipo virus (VLPs con las cuales es posible formular vacunas efectivas y accesibles contra la infección por HPV.Human papillomaviruses (HPV are the etiologic agent for cervical cancer (CC, the second cause of cancer death in women worldwide. It is estimated that half a million new cases are diagnosed each year, mostly in developing countries due to the lack of massive programs for early detection of the virus. Recently, two prophylactic vaccines against the main oncogenic HPV types 16 and 18 (responsible for 80% of CC have been introduced into market. Both of these vaccines, obtained as recombinants, have been shown to be safe and effective; however, their high cost works against its immediate impact in the incidence of HPV infection in developing and low-income countries. There is a need to have in hand second generation, low cost vaccines of massive use

Modelo de detección de anticuerpos neutralizantes contra IFN-β mediante citometría de flujo

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Juan Carlos Villa-Camacho

2012-12-01

Full Text Available Introducción. El interferón beta (IFN-β se usa para tratar la forma recaída-remisión de la esclerosis múltiple. Sin embargo, el uso de proteínas recombinantes como medicamentos puede generar la producción de anticuerpos, disminuyendo así la efectividad del tratamiento. Objetivo. Estandarizar una técnica de detección de anticuerpos neutralizantes contra IFN-β, mediante citometría de flujo. Materiales y métodos. Se cultivaron dos líneas tumorales humanas (U937 y K562 con IFN-β1a humano recombinante y mediante citometría de flujo se determinó la expresión de la proteína ISG15 intracelular. Los sueros se obtuvieron de un conejo Nueva Zelanda antes y después de la inmunización con 100.000 UI de IFN-β1a en adyuvante de Freund. Para la detección de anticuerpos neutralizantes, se estimularon células K562 con IFN-β1a preincubado con sueros de conejos a una dilución 1:20. Después de 24 horas de incubación se determinó la expresión de la proteína ISG15. Resultados. La expresión de ISG15 fue mayor en células K562 estimuladas. La intensidad media de fluorescencia para la ISG-15 entre células en ausencia IFN-β1a, mostró una mediana de 198 unidades arbitrarias (UA (p25-75= 173-231 UA y, en presencia de IFN-β1a, 430 UA (p25-75 =316-611,5, con una diferencia estadísticamente significativa (p=0,008. La presencia de anticuerpos anti-IFN-β1a en el suero del conejo inmunizado, hizo disminuir de forma acentuada la expresión de la ISG15 en células K562 cultivadas con IFN-β1a, en comparación con el control (mediana=3,040 UA Vs. 43,644 UA, respectivamente. Conclusiones. Este trabajo muestra la detección de anticuerpos neutralizantes contra IFN-β en conejos, utilizando la expresión de la proteína ISG15 por citometría de flujo.   doi: http://dx.doi.org/10.7705/biomedica.v32i4.637

Risk Factors

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... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model

Science.gov (United States)

Bell, Angela D.; Hurtig, Mark B.; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D.

2016-01-01

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan–NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro–computed tomography after 1 day (n = 1) and 6 months (n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage. PMID:28934884

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.

Science.gov (United States)

Bell, Angela D; Hurtig, Mark B; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D

2017-10-01

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.

Determining the Number of Factors in P-Technique Factor Analysis

Science.gov (United States)

Lo, Lawrence L.; Molenaar, Peter C. M.; Rovine, Michael

2017-01-01

Determining the number of factors is a critical first step in exploratory factor analysis. Although various criteria and methods for determining the number of factors have been evaluated in the usual between-subjects R-technique factor analysis, there is still question of how these methods perform in within-subjects P-technique factor analysis. A…

Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft.

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Christi M Terry

Full Text Available Hemodialysis arteriovenous synthetic grafts (AVG provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study's objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis

Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

Science.gov (United States)

Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

2010-11-01

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

Identification, cloning and lactonase activity of recombinant protein of N-acyl homoserine lactonase (AiiA from Bacillus thuringiensis 147-115-16 strain.

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Alvaro Mauricio Florez Escobar

2014-01-01

interrumpiendo el sistema de detección de quórum sensing de bacterias Gram negativas. A partir de una colección de cepas de Bacillus thuringiensis aisladas del filoplano de plantas colombianas que presentaron actividad tóxina contra insectos lepidópteros, 310 fueron probadas para determinar actividad lactonasa mediante el uso de sistemas de biosensores en presencia de N-hexanoilo-L-homoserina lactona (C6-HSL y la N-octanoilo-L-homoserina lactona (C8-HSL sintéticas. De estas cepas, el 251 mostraron actividad para ambas lactonas y de estas, el 57% mostró actividad a C6-HSL y el 43% a C8-HSL. Una cepa de B. thuringiensis- denominada 147-115-16- que mostró alta actividad para C6-HSL y C8-HSL, fue capaz de atenuar los síntomas de la pudrición blanda en rodajas de papa infectadas con Pectobacterium carotovorum. Esta cepa contiene un gen homólogo a aiiA, el cual este fue clonado, secuenciado y expresado en Escherichia coli DE3. La proteína recombinante AiiA147-11516 exhibe actividad para C6-HSL y C8-HSL, así como para N-(β-cetocaproil (3-O-C6-HSL y N-3-oxo-dodecanoil (3-O-C12-HSL. La cepa recombinante en presencia  de P. caratovorum fue capaz de atenuar la infección, sugiriendo que interfiere con la acumulación o respuesta de las señales AHLs. Según estos datos y basados en el reporte previo sobre la actividad hidrolítica de la proteína recombinante AiiA147-11516, esta enzima posee un actividad contra un amplio número de sustratos lo cual sugiere su aplicación en la industria en el control de enfermedades, mediante la transformación de plantas. Palabras clave: Lactones, Quorum sensing, Quorum quenching, Lactonases,  Pectobacterium caratovorum.

Efficacy of a gE-deleted, bovine herpesvirus 1 (BoHV-1 inactivated vaccine Eficácia de uma vacina inativada, gE-deletada, contra o herpesvírus bovino tipo 1 (BoHV-1

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Alessandra D. Silva

2009-07-01

diferencial para BoHV-1, baseada em um recombinante do qual a glicoproteína gE (gE foi deletada (265gE-. No presente trabalho foi realizada a avaliação da eficácia de tal recombinante como vacina inativada. Cinco bovinos soronegativos para BoHV-1 foram vacinadas por via intramuscular no dia 0 e revacinadas 30 dias após com uma vacina inativada com adjuvante oleoso, contendo massa antigênica equivalente a 10(7.0 doses infectantes para 50% dos cultivos celulares (DICC50 de 265gE-. Três animais foram mantidos como controles não vacinados. No dia 60 pós-vacinação, os animais vacinados e controles foram desafiados com a amostra virulenta parental. Nenhum sinal clínico ou efeito adverso foi observado após ou durante a vacinação. Após o desafio, 2 dos 5 animais vacinados apresentaram sinais leves de infecção, enquanto que todos os animais não vacinados apresentaram intensa rinotraqueíte e disseminaram vírus por mais tempo e em títulos mais elevados do que os animais vacinados. Respostas sorológicas foram detectadas em todos os animais vacinados depois da segunda dose de vacina, mas não nos animais do grupo controle. Após a administração de corticosteróide visando a reativação de infecções latentes, não foram observados sinais clínicos em nenhum dos 5 animais vacinados, enquanto os animais não vacinados apresentaram sinais leves de doença respiratória. Em vista de sua imunogenicidade e efeito protetor frente ao desafio com BoHV-1 virulento, a preparação oleosa com o recombinante 265gE- inativado foi demonstrada ser adequada para uso como vacina.

Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

Science.gov (United States)

Opgenorth, A; Nation, N; Graham, K; McFadden, G

1993-02-01

The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

Factor concentrates for the treatment of factor XIII deficiency.

Science.gov (United States)

Gootenberg, J E

1998-11-01

Factor XIII deficiency is a severe autosomal recessive bleeding disorder associated with a characteristic pattern of neonatal hemorrhage and a lifelong bleeding diathesis. Even relatively minor trauma can be followed by prolonged and recurrent bleeding. Intracranial hemorrhage is a frequent complication. With the development of safe and effective factor XIII concentrates, reliable prophylactic treatment is possible. Two plasma-derived, virus-inactivated factor XIII concentrates are currently in production. The first, Fibrogammin P, (Centeon LLC, King of Prussia, PA, USA; and Centeon Pharma GmbH, Marburg, Germany) is marketed in Europe, South America, South Africa, and Japan. It is distributed in the United States under a Food and Drug Administration Investigational New Drug Application. A second factor XIII concentrate (Bio Products Laboratory, Elstree, UK) is available for use only on a "named patient" compassionate basis in the United Kingdom. Patients with factor XIII deficiency who receive appropriately timed periodic infusions of such factor XIII concentrates are able to live normal lives, free from catastrophic bleeding episodes.

Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

DEFF Research Database (Denmark)

Bor, M V; Sørensen, B S; Vinter-Jensen, L

2000-01-01

BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

[Coagulation factor VII levels in uremic patients and theirs influence factors].

Science.gov (United States)

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

N,N'-dihydroxyamidines: a new prodrug principle to improve the oral bioavailability of amidines.

Science.gov (United States)

Reeh, Christiane; Wundt, Judith; Clement, Bernd

2007-12-27

N, N'-dihydroxybenzamdine represents a model compound for a new prodrug principle to improve the oral bioavailability of drugs containing amidine functions. The activation of the prodrug could be demonstrated in vitro by porcine and human subcellular enzyme fractions, the mitochondrial benzamidoxime reducing system, and porcine hepatocytes. In vivo, the bioavailability of benzamidine after oral application of N, N'-dihydroxybenzamidine was about 91% and exceeded that of benzamidine after oral application of benzamidoxime, being about 74% (Liu, L.; Ling, Y.; Havel, C.; Bashnick, L.; Young, W.; Rai, R.; Vijaykumar, D.; Riggs, J. R.; Ton, T.; Shaghafi, M.; Graupe, D.; Mordenti, J.; Sukbuntherng, J. Species comparison of in vitro and in vivo conversion of five N-hydroxyamidine prodrugs of fVIIA inhibitors to their corresponding active amidines. Presented at the 13th North America ISSX Meeting, Maui, HI, 2005).

External Factors, Internal Factors and Self-Directed Learning Readiness

Science.gov (United States)

Ramli, Nurjannah; Muljono, Pudji; Afendi, Farit M.

2018-01-01

There are many factors which affect the level of self-directed learning readiness. This study aims to investigate the relationship between external factors, internal factors and self-directed learning readiness. This study was carried out by using a census method for fourth year students of medical program of Tadulako University. Data were…

A factor analysis to detect factors influencing building national brand

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Naser Azad

Full Text Available Developing a national brand is one of the most important issues for development of a brand. In this study, we present factor analysis to detect the most important factors in building a national brand. The proposed study uses factor analysis to extract the most influencing factors and the sample size has been chosen from two major auto makers in Iran called Iran Khodro and Saipa. The questionnaire was designed in Likert scale and distributed among 235 experts. Cronbach alpha is calculated as 84%, which is well above the minimum desirable limit of 0.70. The implementation of factor analysis provides six factors including “cultural image of customers”, “exciting characteristics”, “competitive pricing strategies”, “perception image” and “previous perceptions”.

Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study

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Gonzalez-Toledo Eduardo

2007-10-01

Full Text Available Abstract Background The presence of antiphospholipid antibodies (APLA in multiple sclerosis (MS patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA. Methods A consecutive cohort of 24 subjects with relapsing-remitting (RR MS were studied of whom 7 were in remission (Rem and 17 in exacerbation (Exc. All subjects were examined and underwent MRI of brain. Patients' plasma was tested by standard ELISA for the presence of both IgM and IgG antibodies using a panel of 6 targets: cardiolipin (CL, β2 glycoprotein I (β2GPI, Factor VII/VIIa (FVIIa, phosphatidylcholine (PC, phosphatidylserine (PS and phosphatidylethanolamine (PE. Results In exacerbation up to 80% of MS subjects had elevated titers of IgM antibodies directed against the above antigens. However, in remission, less than half of MS patients had elevated titers of IgM antibodies against one or more of the above antigens. This difference was significant, p Conclusion The findings of this preliminary study show that increased APLA IgM is associated with exacerbations of MS. Currently, the significance of this association in pathogenesis of MS remains unknown. However, systematic longitudinal studies to measure APLA in larger cohorts of patients with relapsing-remitting MS, particularly before and after treatment with immunomodulatory agents, are needed to confirm these preliminary findings.

Glanzmann thrombasthenia

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Nurden Alan T

2006-04-01

Full Text Available Abstract Glanzmann thrombasthenia (GT is a rare autosomal recessive bleeding syndrome affecting the megakaryocyte lineage and characterized by lack of platelet aggregation. The molecular basis is linked to quantitative and/or qualitative abnormalities of αIIbβ3 integrin. This receptor mediates the binding of adhesive proteins that attach aggregating platelets and ensure thrombus formation at sites of injury in blood vessels. GT is associated with clinical variability: some patients have only minimal bruising while others have frequent, severe and potentially fatal hemorrhages. The site of bleeding in GT is clearly defined: purpura, epistaxis, gingival hemorrhage, and menorrhagia are nearly constant features; gastrointestinal bleeding and hematuria are less common. In most cases, bleeding symptoms manifest rapidly after birth, even if GT is occasionally only diagnosed in later life. Diagnosis should be suspected in patients with mucocutaneous bleeding with absent platelet aggregation in response to all physiologic stimuli, and a normal platelet count and morphology. Platelet αIIbβ3 deficiency or nonfunction should always be confirmed, for example by flow cytometry. In order to avoid platelet alloimmunisation, therapeutic management must include, if possible, local hemostatic procedures and/or desmopressin (DDAVP administration. Transfusion of HLA-compatible platelet concentrates may be necessary if these measures are ineffective, or to prevent bleeding during surgery. Administration of recombinant factor VIIa is an increasingly used therapeutic alternative. GT can be a severe hemorrhagic disease, however the prognosis is excellent with careful supportive care.

Overview of clinical efficacy and safety of pharmacologic strategies for blood conservation.

Science.gov (United States)

Levy, Jerrold H

2005-09-15

The pharmacologic management of hemostasis in patients undergoing surgery with cardiopulmonary bypass is discussed. Nearly 45 studies involving 7,000 patients have reported efficacy of aprotinin in blood conservation. Both in primary coronary artery bypass graft (CABG) surgeries and in repeat surgeries, aprotinin treatment significantly reduces the incidence of blood transfusions and the number of units of blood transfused. These effects have been observed for red blood cell, platelet, and other blood products. The safety of aprotinin treatment has been extensively evaluated in randomized clinical trials, in postmarketing databases, and in systematic reviews of the literature. Overall, data do not indicate that aprotinin treatment increases mortality, myocardial infarction, or renal failure. These findings are supported by the results of a recent meta-analysis of 35 studies in patients undergoing CABG surgery. In addition, the meta-analysis suggests that aprotinin treatment was associated with a reduced incidence of stroke and a trend toward a reduced incidence of atrial fibrillation. Although lysine analogs, desmopressin, and recombinant factor VIIa are sometimes used to reduce bleeding, only aprotinin is indicated for use during CABG surgery. The future of cardiac surgery will be marked by an increasingly complex, high-risk group of patients and a greater need for multiple pharmacologic options for reducing bleeding. Pharmacologic approaches that attenuate the activation of the hemostatic system and inflammation need to be employed to decrease coagulopathies and the need for allogeneic blood administration.

Identifying the important factors in simulation models with many factors

NARCIS (Netherlands)

Bettonvil, B.; Kleijnen, J.P.C.

1994-01-01

Simulation models may have many parameters and input variables (together called factors), while only a few factors are really important (parsimony principle). For such models this paper presents an effective and efficient screening technique to identify and estimate those important factors. The

Quality factors

International Nuclear Information System (INIS)

Kerr, G.D.

1986-01-01

The quality factor, Q, is a dimensionless modifier used in converting absorbed dose, expressed in rads (or grays), to dose equivalent, expressed in rems (or seiverts). The dose equivalent is used in radiation protection to account for the biological effectiveness of different kinds of radiation. The quality factor is related to both the linear energy transfer (LET) and relative biological effectiveness (RBE). The RBE's obtained from biological experiments depend in a complex way on the observed biological effect, the specific test organism, and the experimental conditions. Judgement is involved, therefore, in the choice of the quality factor. Questions regarding the adequacy of current Q values for neutrons were raised first in a 1980 statement by the National Council on Radiation Protection (NCRP) and later in a 1985 statement by the International Commission on Radiological Protection (ICRP). In 1980, the NCRP alerted the technical community to possible future increases between a factor of three and ten in the Q for neutrons, and in 1985, the ICRP suggested an increase by a factor of two in Q for neutrons. Both the ICRP and NRCP are now recommending essentially the same guidance with regard to Q for neutrons: an increase by a factor of two. The Q for neutrons is based on a large, albeit unfocused, body of experimental data. In spite of the lack of focus, the data supporting a change in the neutron quality factor are substantial. However, the proposed doubling of Q for neutrons is clouded by other issues regarding its application. 33 refs., 4 figs., 6 tabs

Pseudomonas aeruginosa. Vacunas: un reto a la investigación

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Sara C. Esnard

2004-04-01

Full Text Available Pseudomonas aeruginosa, patógeno gramnegativo versátil y oportunista debido a su gran adaptabilidad fisiológica, potencial metabólico y mecanismos de virulencia, es causa frecuente a escala mundial de severas o letales infecciones en pacientes hospitalizados. El empeño por lograr terapias alternativas para prevenir o combatir las infecciones producidas por P. aeruginosa ha ocupado a investigadores de todo el mundo desde la segunda mitad del pasado siglo y actualmente se continúan reportando trabajos que respaldan los ensayos de candidatos vacunales, fundamentalmente a partir de antígenos proteicos, mayoritariamente basados en la construcción de vacunas recombinantes. En este artículo se presenta una revisión de trabajos publicados sobre las investigaciones desarrolladas en diferentes países, con el objetivo de obtener candidatos vacunales para la prevención o tratamiento de las infecciones causadas por Pseudomonas aeruginosa, a partir de la década de los años 50 del siglo XX hasta el 2003.

CONSTRUCCIÓN DE UNA BIBLIOTECA GENÓMICA DE Coffea Arabica Var. COLOMBIA Y EVALUACIÓN CON UNA SECUENCIA HOMÓLOGA A UBIQUITINA

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Elsa Leonor Álvarez Méndez 1, 2,

2004-06-01

Full Text Available Con el fin de buscar secuencias de interés en el genoma de Coffea arabica var. Colombia, se construyó una biblioteca genómica en el vector Lambda FIX II (Stratagene con un tamaño promedio de inserto de 15Kb y con un título de 1,33x106 ufp/ml que representa aproximadamente 3,7 veces el genoma haploide.La biblioteca fue evaluada utilizando como sonda un producto de PCR amplificado con la combinación de iniciadores InhF - R631 y que presenta alta homología con secuencias tipo ubiquitinas de Arabidopsis thaliana y Oriza sativa. Se identificaron dos clones recombinantes (cof-ubi1 y cof-ubi2 que hibridizaron con la sonda tipo ubiquitina. Los resultados obtenidos indican que la biblioteca genómica es adecuada para la identificación de secuencias de interés, mapeo genético y estudios sobre regulación de la expresión de genes.

Factoring in Factor VIII With Acute Ischemic Stroke.

Science.gov (United States)

Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

2015-10-01

There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

Using Bayes factors for multi-factor, biometric authentication

Science.gov (United States)

Giffin, A.; Skufca, J. D.; Lao, P. A.

2015-01-01

Multi-factor/multi-modal authentication systems are becoming the de facto industry standard. Traditional methods typically use rates that are point estimates and lack a good measure of uncertainty. Additionally, multiple factors are typically fused together in an ad hoc manner. To be consistent, as well as to establish and make proper use of uncertainties, we use a Bayesian method that will update our estimates and uncertainties as new information presents itself. Our algorithm compares competing classes (such as genuine vs. imposter) using Bayes Factors (BF). The importance of this approach is that we not only accept or reject one model (class), but compare it to others to make a decision. We show using a Receiver Operating Characteristic (ROC) curve that using BF for determining class will always perform at least as well as the traditional combining of factors, such as a voting algorithm. As the uncertainty decreases, the BF result continues to exceed the traditional methods result.

Electroweak form factors

International Nuclear Information System (INIS)

Singh, S.K.

2002-01-01

The present status of electroweak nucleon form factors and the N - Δ transition form factors is reviewed. Particularly the determination of dipole mass M A in the axial vector form factor is discussed

El factoring

Directory of Open Access Journals (Sweden)

Alberto Rosenthal

1988-04-01

Full Text Available RESUMEN El artículo  presenta, una conceptualización general de lo que es el factoring, el origen del mismo, su evolución y hace una clasificación de los distintos tipos de factoring.

Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

Science.gov (United States)

Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

2017-05-01

High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

Science.gov (United States)

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.