Evaluation of the anti-proliferative effect the extracts of Allamanda blanchetti and A-schottii on the growth of leukemic and endothelial cells

PURPOSE. To investigate the anti-proliferative effect of A. blanchetti and A. schottii extracts. METHODS. The anti-proliferative effect of A. blanchetti and A. schottii ethanolic extracts on K562 leukemic cells as well as on BMEC and HUVEC were evaluated. Phytochemical analysis to identify the possible active components was carried out. RESULTS. The root extract of A. schottii was the most active of them. At 80 mu g/mL, the root extracts showed a cytostatic effect on K562, whereas at 400 mu g/mL, there was a strong cytotoxic effect. Similar cytostatic and cytotoxic effects were seen in the endothelial cells, but at lower doses. The effect of A. schottii root extract on endothelial cells was seen at concentrations ten times lower (8 mu g/mL) than the effect of the A. blanchetti root extract (80 mu g/mL). Phytochemical investigation of different fractions and parts of the plant led to the isolation of several known compounds, some of which are described for the first time in the genus Allamanda, and with previous evidence of anticancer and antitumoral properties. CONCLUSIONS. Our results suggest that both plants studied exhibit cytostatic and cytotoxic activity, but the most active compounds are located in the roots.9220020

Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

<p>Abstract</p> <p>Background</p> <p>Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether <it>NOTCH1 </it>mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.</p> <p>Methods</p> <p>T-ALL subtypes, status of <it>SIL-TAL1 </it>fusion, ectopic expression of <it>TLX3</it>, and mutations in <it>FBXW7</it>, <it>KRAS</it>, <it>PTEN </it>and <it>NOTCH1 </it>were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.</p> <p>Results</p> <p>The frequencies of mutations were 43.5% for <it>NOTCH1</it>, while <it>FBXW7</it>, <it>KRAS </it>and <it>PTEN </it>exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of <it>NOTCH1 </it>mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between <it>NOTCH1 </it>mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. <it>SIL-TAL1 </it>was identified as an adverse prognostic factor. <it>NOTCH1 </it>mutation status was not associated with outcome, while the presence of <it>NOTCH1 </it>complex mutations (indels) were associated with a longer overall survival (<it>p </it>= 0.031) than point mutations.</p> <p>Conclusion</p> <p><it>NOTCH1 </it>mutations alone or in combination with <it>FBXW7 </it>did not impact T-ALL prognosis. Nevertheless, complex <it>NOTCH1 </it>mutations appear to have a positive impact on OS and the <it>SIL-TAL1 </it>fusion was validated as a negative prognostic marker in our series of T-ALL.</p

A nontoxic polypeptide oligomer with a fungicide potency under agricultural conditions which is equal or greater than that of their chemical counterparts

Research ArticleThere are literally hundreds of polypeptides described in the literature which exhibit fungicide activity. Tens of them have had attempted protection by patent applications but none, as far as we are aware, have found application under real agricultural conditions. The reasons behind may be multiple where the sensitivity to the Sun UV radiation can come in first place. Here we describe a multifunctional glyco-oligomer with 210 kDa which is mainly composed by a 20 kDa polypeptide termed Blad that has been previously shown to be a stable intermediary product of β-conglutin catabolism. This oligomer accumulates exclusively in the cotyledons of Lupinus species, between days 4 and 12 after the onset of germination. Blad-oligomer reveals a plethora of biochemical properties, like lectin and catalytic activities, which are not unusual per si, but are remarkable when found to coexist in the same protein molecule. With this vast range of chemical characteristics, antifungal activity arises almost as a natural consequence. The biological significance and potential technological applications of Blad-oligomer as a plant fungicide to agriculture, its uniqueness stems from being of polypeptidic in nature, and with efficacies which are either equal or greater than the top fungicides currently in the market are addressedinfo:eu-repo/semantics/publishedVersio

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Increased CCL2 and IL-8 in the Bone Marrow Microenvironment in Acute Lymphoblastic Leukemia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background. The interactions of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells have a positive impact on leukemia cell survival. In the present study, we proposed to identify and investigate the role of molecules critically involved in leukemia-microenvironment crosstalk. Procedure. Gene expression profiling analyses of BM mesenchymal stem cells (BMMSC) were performed following stimulation by ALL cells. CCL2 and IL-8 plasma levels were evaluated from, ALL patients and controls. Expression of the CCL2 and IL-8 receptors in ALL was determined by RT-PCR. The biological effects of CCL2, IL-8 or its neutralizing antibodies in primary precursor-B ALL and BMMSC cells were evaluated using in vitro assays. Results. Leukemia stimulation of BMMSC upregulated the expression of several inflammatory chemokines, including CCL2 and IL-8. The BM plasma levels of CCL2 and IL-8 in children at diagnosis were significantly higher than in healthy controls (P < 0.00)). Functional studies revealed that CCL2 and IL-8 enhanced the capacity of BMMSC to support adhesion of ALL cells. CCL2 and IL-8 were also found to enhance BMMSC survival and to increase their proliferation. ALL cells were not directly affected by CCL2 or IL-8. Conclusions. The leukemic BM microenvironment had increased levels of CCL2 and IL-8. These chemokines are known to have suppressive effects in normal hematopoiesis. Our data indicate that CCL2 and IL-8 have a positive impact on BMMSC survival, proliferation, and adhesiveness to ALL cells. Leukemia-associated CCL2 and IL-8 upregulation may represent one possible mechanism of microenvironment perversion in favor of ALL cells. Pediatr Blood Cancer 2011;56:568-577. (C) 2010 Wiley-Liss, Inc.564568577Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [05/02390-4, 06/02083-7, 06/01158-3, 08/02106-2]CNPq [401122/05, 382.687/2008-6

A resiliência como objeto de investigação na enfermagem e em outras áreas: uma revisão La resiliencia como objeto de investigación en la enfermería y en otras areas: una revisión Resilience as subject for investigation in nursing and in other areas: a revision

Estudo descritivo quantiqualitativo na modalidade de revisão sistemática em bases de dados, tendo, como descritores, Resiliência e Enfermagem. Os dados foram caracterizados pela freqüência em cada área de conhecimento. Objetivamos buscar, no catálogo do CEPEN e nas bases eletrônicas de dados BDENF, LILACS, MEDLINE, SCIELO, a resiliência como temática nas produções da Enfermagem, entre janeiro de 1993 e maio de 2004. A incidência foi encontrada nas Ciências Sociais. No MEDLINE, a maior concentração deu-se na Saúde Mental. No BDENF, sua abordagem é escassa. No SCIELO, a Psicologia concentrou os estudos sobre o tema. Dos 122 estudos analisados, a resiliência foi objeto em 6% do total dos estudos. Verificamos uma lacuna na utilização do conceito na área da Enfermagem Latino-Americana, fato que agrega valor ao estudo, contribuindo para um redimensionamento do cotidiano profissional.<br>Estudio descriptivo cualitativo y cuantitativo en la modalidad de la revisión sistemática en bases de datos, teniendo, como descritores, Resiliencia y Enfermería. Los datos fueron caracterizados por la frecuencia en cada área del conocimiento. Objectivamos buscar, en el catálogo del CEPEN y las bases electrónicas de datos BDENF, LILACS, MEDLINE, SCIELO, la resiliencia como temática en las producciones de enfermería, entre enero de 1993 y mayo de 2004. La incidencia fué encontrada en las Ciencias Sociales. En el MEDLINE, la concentración más grande fue dada en la Salud Mental. En el BDENF, el abordaje es escaso. En el SCIELO, la Psicología concentró los estudios sobre el tema. De los 122 estudios analizados, la resiliencia era objeto en el 6% del total de los estudios. Verificamos una laguna en el uso del concepto en el área de Enfermera Latinoamericana, el hecho que agrega valor al estudio, contribuyendo para redimensionamiento del cotidiano profesional.<br>Qualitative and quantitative descriptive study in the modality of systematic revision in databases, having, as describing, Resilience and Nursing. The data was characterized by the frequency in each area of knowledge. We objectify to search, in the catalogue of the CEPEN and the electronic bases of data BDENF, LILACS, MEDLINE, SCIELO, the resilience as thematic in the productions of the Nursing, between January of 1993 and May of 2004. The incidence was found in Social Sciences. In the MEDLINE, the biggest concentration it was given in the Mental Health. In the BDENF, its boarding is scarce. In the SCIELO, the Psychology concentrated the studies about the thematics. From the 122 analyzed studies, the resilience was object in 6% of the total of the studies. We verify a gap in the use of the concept in the area of the Latin American Nursing, fact that adds value to the study, contributing for a redimensionning of the daily professional