931 resultados para ARA-BY15
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We discuss necessary as well as sufficient conditions for the second iterated local multiplier algebra of a separable C*-algebra to agree with the first.
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Better treatment is required for older patients with acute myeloid leukemia (AML) not considered fit for intensive chemotherapy. We report a randomized comparison of lowdose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406 patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10% marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice daily for 10 days every 6 weeks or clofarabine 20 mg/m2 on days 1 to 5, both for up to 4 courses. These patients had more adverse demographics than contemporaneous intensively treated patients. The overall remission rate was 28%, and 2-year survival was 13%. Clofarabine significantly improved complete remission (22% vs 12%; hazard ratio [HR] 5 0.47 [0.28-0.79]; P 5 .005) and overall response (38% vs 19%; HR 5 0.41 [0.26-0.62]; P < .0001), but there was no difference in overall survival, explained by poorer survival in the clofarabine patients who did not gain complete remission and also following relapse. Clofarabine was more myelosuppressive and required more supportive care. Although clofarabine doubled remission rates, overall survival was not improved overall or in any subgroup. The treatment of patients of the type treated here remains a major unmet need. This trial was registered at www.clinicaltrials.gov as #ISRCTN 11036523.
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Two hundred eighty-five patients, median age 42, with PML-RARa-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, P10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.
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Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.
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Expression of the transforming oncogene bcr-abl in chronic myelogenous leukemia (CML) cells is reported to confer resistance against apoptosis induced by many chemotherapeutic agents such as etoposide, ara-C, and staurosporine. In the present study some members of a series of novel pyrrolo-1,5-benzoxazepines potently induce apoptosis, as shown by cell shrinkage, chromatin condensation, DNA fragmentation, and poly(ADP-ribose) polymerase (PARP) cleavage, in three CML cell lines, K562, KYO.1, and LAMA 84. Induction of apoptosis by a representative member of this series, PBOX-6, was not accompanied by either the down-regulation of Bcr-Abl or by the attenuation of its protein tyrosine kinase activity up to 24 h after treatment, when approximately 50% of the cells had undergone apoptosis. These results suggest that down-regulation of Bcr-Abl is not part of the upstream apoptotic death program activated by PBOX-6. By characterizing the mechanism in which this novel agent executes apoptosis, this study has revealed that PBOX-6 caused activation of caspase 3-like proteases in only two of the three CML cell lines. In addition, inhibition of caspase 3-like protease activity using the inhibitor z-DEVD-fmk blocked caspase 3-like protease activity but did not prevent the induction of apoptosis, suggesting that caspase 3-like proteases are not essential in the mechanism by which PBOX-6 induces apoptosis in CML cells. In conclusion, this study demonstrates that PBOX-6 can bypass Bcr-Abl-mediated suppression of apoptosis, suggesting an important potential use of these compounds in the treatment of CML.
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Objective: To study the population distribution and longitudinal changes in anterior chamber angle width and its determinants among Chinese adults. Design: Prospective cohort, population-based study. Participants: Persons aged 35 years or more residing in Guangzhou, China, who had not previously undergone incisional or laser eye surgery. Methods: In December 2008 and December 2010, all subjects underwent automated keratometry, and a random 50% sample had anterior segment optical coherence tomography with measurement of angle-opening distance at 500 μm (AOD500), angle recess area (ARA), iris thickness at 750 μm (IT750), iris curvature, pupil diameter, corneal thickness, anterior chamber width (ACW), lens vault (LV), and lens thickness (LT) and measurement of axial length (AL) and anterior chamber depth (ACD) by partial coherence laser interferometry. Main Outcome Measures: Baseline and 2-year change in AOD500 and ARA in the right eye. Results: A total of 745 subjects were present for full biometric testing in both 2008 and 2010 (mean age at baseline, 52.2 years; standard deviation [SD], 11.5 years; 53.7% were female). Test completion rates in 2010 varied from 77.3% (AOD500: 576/745) to 100% (AL). Mean AOD500 decreased from 0.25 mm (SD, 0.13 mm) in 2008 to 0.21 mm (SD, 13 mm) in 2010 (difference, -0.04; 95% confidence interval [CI], -0.05 to -0.03). The ARA decreased from 21.5±3.73 10-2 mm2 to 21.0±3.64 10 -2 mm2 (difference, -0.46; 95% CI, -0.52 to -0.41). The decrease in both was most pronounced among younger subjects and those with baseline AOD500 in the widest quartile at baseline. The following baseline variables were significantly associated with a greater 2-year decrease in both AOD500 and ARA: deeper ACD, steeper iris curvature, smaller LV, greater ARA, and greater AOD500. By using simple regression models, we could explain 52% to 58% and 93% of variation in baseline AOD500 and ARA, respectively, but only 27% and 16% of variation in 2-year change in AOD500 and ARA, respectively. Conclusions: Younger persons and those with the least crowded anterior chambers at baseline have the largest 2-year decreases in AOD500 and ARA. The ability to predict change in angle width based on demographic and biometric factors is relatively poor, which may have implications for screening. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.
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As galactomananas das infusões de café apresentam atividade imunoestimuladora in vitro, sendo esta atividade semelhante à das mananas acetiladas extraídas de Aloe vera. As galactomananas presentes no resíduo de café também possuem atividade imunoestimuladora in vitro quando são parcialmente acetiladas. Como as galactomananas são o componente maioritário do resíduo de café e como o café é um produto de largo consumo a nível mundial, o reaproveitamento deste resíduo como fonte de galactomananas com atividade imunoestimuladora deve ser considerado. Esta dissertação procura dar resposta a duas questões: 1. Quais são as estruturas das galactomananas responsáveis pela atividade imunoestimuladora destes polissacarídeos; e 2. Como é que as galactomananas podem ser extraídas quantitativamente do resíduo de café de modo a serem solúveis em água à temperatura ambiente e, assim, poderem ser utilizadas como ingredientes alimentares com atividade imunoestimuladora. A questão 1 foi respondida pela caracterização estrutural de quatro galactomananas, de três origens: a) as galactomananas das infusões de café e do resíduo que apresentaram atividade imunoestimuladora; b) a galactomanana da goma de alfarroba (LBG), que não apresentou atividade imunoestimuladora; e c) a manana acetilada de Aloe vera, que apresentou atividade imunoestimuladora. Estes polissacarídeos foram submetidos à análise de açúcares e de ligações glicosídicas e a hidrólise por endo-β-D- (1→4)-mananase. Os fragmentos de oligossacarídeos mais pequenos foram ainda analisados por espetrometria de massa por ionização de electrospray e espetrometria de massa tandem. As galactomananas das infusões de café, do resíduo de café e do Aloe vera apresentaram grau de ramificação e peso molecular semelhantes, enquanto as galactomananas da LBG apresentaram grau de ramificação e de polimerização maiores. Todas as galactomananas apresentaram resíduos de arabinose como ramificação. O grau de acetilação das galactomananas da LBG foi vestigial enquanto as galactomananas do Aloe vera apresentaram um grau de acetilação de 2,08; para as galactomananas do resíduo de café o grau de acetilação foi de 0,98 e para as infusões foi de 0,08. A localização dos grupos acetilo foi irregular em todos os polímeros. Os resultados obtidos permitem inferir que baixos níveis de ramificação, cadeias pequenas e alguma acetilação parecem promover a atividade imunoestimuladora atribuída às galactomananas. Para responder à questão 2, foi testada uma metodologia que envolveu a torra do resíduo de café a 160 ºC e a 220 ºC e a sua extração com água quente e com soluções de 4 M NaOH à temperatura de 20, 60 e 120 ºC. A torra do resíduo a 160 ºC e a extração sequencial permitiu extrair 56% das galactomananas presentes no resíduo de café e, simultaneamente, 54% das arabinogalactanas. As galactomananas mantiveram a sua estrutura caraterística de polissacarídeo acetilado composto por uma cadeira principal de resíduos de manose em ligação β-(1→4) e resíduos de Gal e Ara nas cadeias laterais. A 220 ºC, as galactomananas foram parcialmente degradadas e o rendimento de extração foi muito menor do que a 160 ºC. No entanto, mesmo a esta temperatura as galactomananas apresentaram resíduos acetilados e a presença de pentoses nas cadeias laterais, o que permite inferir a elevada resistência destes polissacarídeos à temperatura e aos reagentes alcalinos. De forma a melhor compreender a estabilidade térmica das galactomananas do resíduo de café e a influência que a presença de arabinogalactanas pode ter na sua estabilidade, foi feita uma análise termogravimétrica aos polissacarídeos extraídos do resíduo de café assim como a polissacarídeos relacionados estruturalmente com estes, como a celulose, a galactomanana de LBG e a goma arábica, uma arabinogalactana. As galactomananas são termicamente estáveis durante 3 h a 200 ºC, enquanto as arabinogalactanas são estáveis a 180 ºC. De acordo com os perfis dos termogramas obtidos, e pelo cálculo das energias de ativação da degradação térmica, o resíduo de café apresenta uma estabilidade térmica menor do que a galactomanana, possivelmente devido à presença de arabinogalactanas. Apesar de não se ter verificado alterações no termograma da galactomanana do café submetida a um tratamento térmico de 200 ºC durante 3 h, verificam-se alterações estruturais que envolvem a formação de novas ligações glicosídicas, nomeadamente, a formação de resíduos de manose ligados em O-2 e em O-6, reações de transglicosilação, despolimerização, formação de resíduos de anidro-hexoses no terminal redutor e isomerização manose-glucose. Estas alterações promovem a solubilização das galactomananas. Os resultados obtidos permitem propor que o resíduo de café possa ser submetido a uma torra seguida de extração com reagentes alcalinos a quente para obtenção das galactomananas com rendimentos elevados. Estes polissacarídeos podem tornar-se solúveis em água após tratamento térmico a 200 ºC, permitindo assim a sua utilização em formulações alimentares, nomeadamente, por preparação de compostos acetilados com baixos níveis de ramificação e cadeias pequenas de modo a promover a sua atividade imunoestimuladora.
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Dissertação de Mestrado, Biologia Marinha, especialização em Pescas e Aquacultura, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2009
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Dissertação mest., Aquacultura e Pescas, Universidade do Algarve, 2009
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Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum coreanum (Lévl.) Rapaics have shown anti-inflammatory activity, which is strongly influenced by their chemical structures and chain conformations. However, the mechanisms of the anti-inflammatory effect by these polysaccharides have yet to be elucidated. A RG-II polysaccharide (KMPS-2E, Mw 84.8 kDa) was isolated from KMPS and its chemical structure was characterized by FT-IR and NMR spectroscopy, gas chromatography–mass spectrometry and high-performance liquid chromatography. The backbone of KMPS-2E consisted of units of [→6) -β-D-Galp (1→3)-β-L-Rhap-(1→4)-β-D-GalpA-(1→3)-β-D-Galp-(1→] with the side chain →5)-β-D-Arap (1→3, 5)-β-D-Arap (1→ attached to the backbone through O-4 of (1→3,4)-L-Rhap. T-β-D-Galp is attached to the backbone through O-6 of (1→3,6)-β-D-Galp residues and T-β-D-Ara is connected to the end group of each chain. The anti-inflammatory effects of KMPS-2E and the underlying mechanisms using lipopolysaccharide (LPS) - stimulated RAW 264.7 macrophages and carrageenan-induced hind paw edema were investigated. KMPS-2E (50, 100 and 200 µg/mL) inhibits iNOS, TLR4, phospho-NF-κB–p65 expression, phosphor-IKK, phosphor-IκB-α expression as well as the degradation of IκB-α and the gene expression of inflammatory cytokines (TNF-α, IL-1β, iNOS and IL-6) mediated by the NF-κB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced activation of NF-κB as assayed by electrophorectic mobility shift assay (EMSA) in a dose-dependent manner and it reduced NF-κB DNA binding affinity by 62.1% at 200µg/mL. In rats, KMPS-2E (200 mg/kg) can significantly inhibit carrageenan-induced paw edema as ibuprofen (200 mg/kg) within 3 h after a single oral dose. The results indicate that KMPS-2E is a promising herb-derived drug against acute inflammation.
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Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo Energia
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A gold nanoparticle-coated screen-printed carbon electrode was used as the transducer in the development of an electrochemical immunosensor for Ara h 1 (a major peanut allergen) detection in food samples. Gold nanoparticles (average diameter=32 nm) were electrochemically generated on the surface of screen-printed carbon electrodes. Two monoclonal antibodies were used in a sandwich-type immunoassay and the antibody–antigen interaction was electrochemically detected through stripping analysis of enzymatically (using alkaline phosphatase) deposited silver. The total time of the optimized immunoassay was 3 h 50 min. The developed immunosensor allowed the quantification of Ara h 1 between 12.6 and 2000 ng/ml, with a limit of detection of 3.8 ng/ml, and provided precise (RSD <8.7%) and accurate (recovery >96.6%) results. The immunosensor was successfully applied to the analysis of complex food matrices (cookies and chocolate), being able to detect Ara h 1 in samples containing 0.1% of peanut.
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A problemática do recurso à luta armada para derrubar a ditadura em Portugal gerou discussões, debates e rupturas no seio da oposição portuguesa muito antes de terem surgido as primeiras organizações que realizaram acções armadas. Foi no rescaldo da campanha para as eleições presidenciais de 1958, perante o apoio popular à campanha de Humberto Delgado, candidato da oposição, e a constatação da dimensão da fraude eleitoral, que ocorreram as primeiras discussões acerca da inevitabilidade recorrer à violência armada para derrubar a ditadura. Porém, apenas na década de 70 as circunstâncias políticas, económicas e sociais no país favorecem o aparecimento de outras organizações armadas. Os quase dez anos de guerra colonial tinham desgastado o regime e as manifestações contra a guerra eram cada vez maiores, com o numero de desertores e refractários a crescer de ano para ano. Ao mesmo tempo, o pais ia-se industrializando e terciarizando; assistia-se ao crescimento da classe média, da escolarização, da emigração e a uma mudança de mentalidade, trazida pelo acesso cada vez maior ao que se passava no mundo. Seria neste contexto que as formas tradicionais de oposição, baseadas em manifestações pacíficas e abaixo-assinados, são sentidas como ultrapassadas e ineficazes e começam a proliferar as organizações marxistas-leninistas que teorizavam sobre a luta armada e concebiam planos de acções armadas contra o regime, aumentando o número daqueles que defendiam que o regime só cairia com o recurso à violência. Em 1967, a LUAR, levava a cabo a primeira acção armada contra o regime, o assalto à agência do Banco de Portugal na Figueira da Foz, para obter dinheiro que seria utilizado no financiamento de futuras acções armadas. Em 1970, o Partido Comunista Português, depois de um prolongadíssimo período de maturação, avançava com a ARA que levou a cabo a primeira acção em Outubro desse ano, a sabotagem ao navio Cunene que participa da logística de apoio à guerra colonial. Em 1971, foram as Brigadas Revolucionárias que desencadearam a primeira acção, um atentado bombista contra o Quartel da Nato na Fonte da Telha. Até ao 25 de Abril de 1974, várias acções armadas seriam cometidas por estas organizações, com a particularidade de apenas atingirem o aparelho repressivo e militar do regime, e de seguirem o princípio irredutível de não fazer vítimas mortais entre os civis. O 25 de Abril de 1974, corresponderia ao epílogo de um processo de contestação armada ao Estado Novo que foi acelerando nos seus derradeiros anos.
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La diffusion internationale des paiements pour services environnementaux (PSE) a été interprétée en 2010 par le gouvernement bolivien d'Evo Morales comme une réponse strictement néolibérale à la nécessité d'assurer une gestion durable des ressources naturelles. Supposée amener à terme à l'éviction de toute régulation autre que marchande - qu'elle s'applique à la nature ou aux rapports entre personnes -, la mise en place de PSE n'a pas été encouragée par les autorités nationales boliviennes. Des projets de PSE ont toutefois été lancés, dont les Acuerdos Reciprocos por el Agua (ARA), issus d'un partenariat public-privé dans le département de Santa Cruz. En analysant leur conception et leur fonctionnement au prisme du référentiel polanyien, nous montrons que, contrairement aux craintes gouvernementales, ces PSE ne font pas abstraction des logiques organisationnelles réciprocitaires et redistributives, ajustant au contexte local un objet global. The international dissemination of payments for ecosystem services (PES) has been interpreted in 2010 by the Bolivian government of Evo Morales as a strictly neo-liberal response to the need to ensure a sustainable management of natural resources. Supposed to contribute to the crowding-out of any other regulation than market - applied to the nature or the relationship between people - the implementation of PES was not encouraged by the Bolivian national authorities. However some PES projects stemming from a public-private partnership have been initiated at local level, as the Acuerdos Reciprocos por el Agua (ARA), in the department of Santa Cruz. Analysing their design and operating through the Polanyian framework, we show that, contrary to the government fears, these PES do not ignore the reciprocal and redistributive organisational logics, adjusting a global object to the local context.