Hematopoietic stem cell transplantation in chronic lymphoid leukemia: a proposal by the Brazilian Consensus on Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation, Rio de Janeiro 2009

Portadores de leucemia linfoide crônica (LLC) apresentam curso clínico indolente e prolongado que devem ser diferenciados daqueles que têm doença de evolução agressiva e fatal. Pacientes mais jovens e com critérios de alto risco podem se beneficiar com tratamento mais agressivo como o transplante de células-tronco hemopoéticas (TCTH). O transplante autólogo apresenta casos com remissão citogenética e molecular, baixa taxa de mortalidade, mas não demonstram platô nas curvas de sobrevivência e alta taxa de recaídas. Os transplantes alogênicos com regime mieloablativos têm altos índices de toxicidade e mortalidade, mas evidenciam o efeito enxerto versus leucemia, que aumenta a possibilidade de cura destes indivíduos. Assim, a opção dos transplantes alogênicos está dirigida para os transplantes com regime de condicionamento não mieloablativo, que pode ser aplicado inclusive a pacientes mais idosos ou portadores de comorbidades, e manter o potencial efeito GVL. A identificação dos pacientes que podem ser beneficiados por esses procedimentos, caracterizar e apontar os novos marcadores prognósticos permanece objeto de muitos estudos clínicos e foi o objetivo do grupo responsável em discutir as diretrizes do TCTH no consenso da Sociedade Brasileira de Transplante de Medula Óssea - SBTMO. Assim, consideramos que o TCTH para a leucemia linfoide crônica (LLC) deve seguir, para sua indicação, os critérios do European Group for Blood and Marrow Transplantation (EBMT) e, quando houver disponibilidade de um doador aparentado, a opção deve ser do TCTH alogênico com regime não mieloablativo. O TCTH alogênico não aparentado e o autólogo devem ser considerados como opção secundária de indisponibilidade de doador, situações especiais e ensaios clínicos.Patients with chronic lymphocytic leukemia usually have an indolent and prolonged clinical course and need to be differentiated from those who have an aggressive and fatal disease. Younger patients with high-risk criteria may benefit with a more aggressive treatment that includes hematopoietic stem cell transplantation (HSCT). Autologous transplantation, despite of the encouraging results with cases of molecular and/or cytogenetic remission and low mortality rates, does not present a plateau in survival curves and has a high relapse rate. Allogeneic transplantations using myeloablative regimens, have high toxicity and mortality rates, but also demonstrate the graft-versus-leukemia effect that increases the possibility of cure of these individuals. So the option of allogeneic transplants for patients with CLL is directed to conditioning using non-myeloablative regimens, which can also be applied to older patients or those with comorbidities, and maintain a potential graft-versus-leukemia effect. The identification of patients who may benefit from these procedures and the characterization of new prognostic markers remain the subjects of many clinical studies and were the objective of the group responsible for discussing guidelines for CLL of the consensus on HSCT SBTMO. Thus we believe that HSCT for CLL should follow the criteria of the EBMT. When a sibling donor is available the best option is allogeneic HSCT with a myeloablative regimen. The strategy of unrelated allogeneic or autologous HSCT must be considered as a second option when no donor is available, for special situations and clinical trials

On the experimental study of the interface between a fiber composite lamina and concrete

In order to properly evaluate the failure characteristics and the strength of the bond between concrete and a fiber reinforced polymer (FRP) lamina, it is necessary to study the shear failure of the corresponding interface under different loading conditions. Two test configurations that permit such characterization are discussed here. The first is applicable to thin surface bonded laminas, and the test is performed using two standard concrete cylinders joined by the laminas and subjected to uniaxial tension. The second is applicable to laminates that are bonded on the surface or inserted into cuts made on the surface. The specimen is made up two blocks with a hinge between them and is loaded in bending. The results can help identify the mechanisms that could be of practical interest in structural applications.Spanish Ministry of Science and Technology - grant PB98-0293. Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/3259/2000. Fundo Social Europeu (FSE) - SFRH/BD/3259/2000. CAPES (Brazil). Bettor MBT (Spain)

Soil composite-concrete systems : characterization of the geocomposite-soil interface

O conhecimento dos mecanismos de interacção entre solos e geossintéticos é fundamental para o dimensionamento de obras em solo reforçado. Com o objectivo de caracterizar a interface entre um solo e um geossintético, foram realizados ensaios de corte directo e de arranque de um geocompósito drenante disponível no mercado. Os ensaios de corte directo foram realizados em conformidade com a norma NP EN ISO 12957-1:2007. Para a determinação da resistência do geocompósito ao arranque no solo foi concebida e utilizada uma caixa de arranque em laboratório, tendo os ensaios sido realizados de acordo com os procedimentos referidos na norma NP EN 13738:2007.The knowledge of the interaction mechanism between soils and geosynthetics is crucial for the design of construction in reinforced soil. With the purpose of characterising the mechanical behaviour of the interface between a soil and a geosynthetic, direct shear tests and pullout tests were carried out with a geocomposite available in the market. The direct shear tests were performed in compliance with the NP EN ISO 12957-1:2007 standard. For the determination of the pullout resistance of the geocomposite in the soil, a pullout box was conceived and used in the laboratory, and the tests were carried out in accordance with the NP EN 13738:2007 standard

NMR and molecular modelling studies on elastase inhibitor-peptides for wound management

Proteases play an important and critical role in the physiological process of wound repair. However, excessive and unregulated release of proteolytic enzymes (e.g., elastase) mediates abnormal degradation of healthy tissues, which leads to inflammatory disorders such as chronic wounds. Thus, it is of therapeutic interest to develop novel synthetic inhibitor-peptides of elastase, which can restore the balance between the free enzyme and the endogenous inhibitors in chronic wounds. In previous works, we have reported two different drug delivery systems to release novel elastase inhibitors to the wound site. In both systems synthetic peptides (KRCCPDTCGIKCL-Pep4 and KRMMPDTMGIKML-Pep4M) based on the primary structure of the endogenous elastase inhibitor, secretory leucocyte protease inhibitor, were used as active material. Phosphorylation of the reported peptides prompts significant structural differences, which reflects in distinct inhibitory capacity towards elastase. These structural modifications were prompted by electrostatic interactions and hydrogen bonds established from the peptide phosphoresidue. The current study was also extended to another synthetic peptide (WCTASVPPQCY-PepBBI) that is based on the reactive loop of another elastase inhibitor, the Bowmen-Birk inhibitor. PepBBI, phosphorylated and non-phosphorylated, displays similar behaviour to Pep4 and Pep4M. The structural modifications reported herein were evaluated by two-dimensional nuclear magnetic resonance and molecular modelling approaches.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (scholarship SFRH/BD/36522/2007 and PEst-OE/EQB/LA0004/2011), FEDER (European Fund for Regional Development)-COMPETE-QREN-EU and the European Project Lidwine - Multifunctional medical textiles for wound (e.g. Decubitus). We acknowledge CERMAX at ITQB-UNL and Rede Nacional de RMN for access to the facilities. Rede Nacional de RMN is supported with funds from FCT, Projecto de Re-equipamento Cientifico contract REDE/1517/RMN/2005, Portugal. Micaelo, N.M. acknowledges the contract research program "Compromisso corn a Ciencia" reference: C2008-UMINHO-CQ-03 and access to the Minho University GRIUM cluster

Soil composite-concrete systems : characterization of geocomposite-concrete interface

Com o objectivo de caracterizar mecanicamente a interface entre um geocompósito, disponível no mercado, e um tipo de betão procedeu-se a um programa de ensaios experimentais. Este estudo foi iniciado com a realização de ensaios de determinação das propriedades em tracção do geocompósito, em conformidade com a norma NP EN ISO 10319:2005. A caracterização da ligação entre geocompósito e betão foi efectuada com recurso a ensaios de arranque directo, com diferentes níveis de tensão de confinamento, no sentido de ser obtida a envolvente de rotura da interface. Neste trabalho, a metodologia e os procedimentos adoptados nos diversos ensaios são descritos e os principais resultados obtidos são apresentados e analisados.In order to characterize the mechanical interface between a geocomposite available in the market and a type of concrete, an experimental program was carried out. This study was initiated with a series of tests for the determination of the tensile properties of the geocomposite, according to the NP EN ISO 10319:2005 standard. The characterization of bond between geocomposite and concrete was carried out using direct pullout tests with different levels of confinement, in order to define the yield surface of the interface. In this work the methodology and procedures followed in the different experimental tests are described and the main results are presented and analysed

Clinical Study Intraoperative Full-Dose of Partial Breast Irradiation with Electrons Delivered by Standard Linear Accelerators for Early Breast Cancer

is properly cited. Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with invasive ductal carcinoma ( ≤ 3.0 cm) at low risk for local relapses were treated. All had unicentric lesions by imaging methods and negative sentinel node. After a wide local excision, 21 Gy were delivered on the parenchyma target volume with electron beams. Local recurrences (LR), survival, toxicity, and cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40-85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The cumulative incidence rates of LR, distant metastases, and BC death were 3.2%, 1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results were excellent or good in most of the patients. Conclusions. IORT with electrons delivered by standard Linacs is feasible, efficient, and well tolerated and seems to be beneficial for selected patients with early infiltrating BC

Survival and Histopathological Study of Animals Bearing Ehrlich Tumor Treated With a Rhodium(II) Amidate

The survival of 90% of a tumor-bearing population treated with the complex Rh2 (CF3CONH)4 was examined and the pharmacological parameter Surv90 determined. Histopathological alterations raised for this drug in several tissues were studied in Balb-c mice. A Surv90 dose of 3.8x 10-5 mol/kg was found

Evaluation of the effect of hypothermia by cold water immersion on blood neutrophils and lymphocytes of rats submitted to acute exercise

O estresse sistêmico induzido pelo exercício libera substâncias bioativas determinantes da mobilização neutrofílica. A crioterapia diminui a reação inflamatória e atenua a elevação da perfusão sanguínea induzida pelo exercício. O objetivo deste trabalho foi analisar a influência da hipotermia decorrente da crioimersão corporal (CIC) imediata ao esforço físico agudo nas concentrações neutrofílicas e linfocíticas no sangue. Os ratos do grupo controle (AI) foram mantidos em repouso enquanto os do grupo AII foram submetidos ao protocolo de CIC a 10ºC por 10 minutos. Enquanto os animais dos grupos BI, BII, BIII e BIV realizaram o esforço físico agudo (EFA) em água a 31ºC durante 100 minutos com sobrecarga corpórea de 5% do peso corporal, os dos grupos CI, CII, CIII e CIV foram submetidos ao EFA seguido imediatamente de CIC. Nos grupos B e C, os animais foram sacrificados nos períodos de 06 (I), 12 (II), 24 (III) e 48 (IV) horas posteriores ao EFA. Através da microscopia óptica realizou-se a contagem dos neutrófilos e linfócitos. Utilizou-se do Teste T Student para análise estatística considerando-se nível de significância p < 0,05. Observou-se uma significativa neutrofilia nos grupos AII, BI, BII, BIII, BIV, CI, CII e CIII em relação a AI, diferentemente do grupo CIV, que apresentou quantidade de neutrófilos igual ao grupo controle. Os valores de linfócitos nos grupos BII, BIII, BIV, CI e CII foram significativamente menores do que AI, e nos grupos AII, BI, CIII e CIV foram iguais a AI. A neutrofilia e a linfopenia posteriores ao intenso exercício agudo são mantidas por 48 horas ou mais, porém, mediante a aplicação da crioimersão corporal imediata ao exercício, são normalizadas em 24 horas.Systemic stress induced by exercise increases bioactive substances in plasma which leads to neutrophilic mobilization. Cryotherapy causes a decrease in the inflammatory reaction and attenuates high blood perfusion after exercise. The objective of this work was to analyze the influence of cold water immersion (CWI) after acute exercise on neutrophil and lymphocyte mobilization. A control group of rats (AI) was kept at rest and a second group (AII) was submitted to CWI at 10º C for 10 minutes. The animals of Groups BI, BII, BIII and BIV were submitted to acute exercise which consisted in swimming in water at 31º C for 100 minutes with a load equivalent to 5% of the body weight. Groups CI, CII, CIII and CIV were submitted to CWI immediately after acute exercise. The animals were sacrificed at 6 (I), 12 (II), 24 (III) and 48 (IV) hours after the exercise and neutrophil and lymphocyte cells were counted for all groups by optic microscopy. The Student t-test was used for statistical analysis with a significance level of p< 0.05. A significant increase in the number of neutrophils was observed in Groups AII, BI, BII, BIII, BIV, CI, CII and CIII compared to AI. The neutrophil count of the CIV Group was similar to the Control Group. There was a significant drop in the number of lymphocytes in Groups BII, BIII, BIV, CI and CII when compared to Group AI. The lymphocyte count of Groups AII, BI, CIII and CIV were similar to the Control Group. The changes in neutrophil and lymphocyte counts caused by acute exercise were reverted to normal at 24 hours by cold water immersion

Modified Brans-Dicke theory of gravity from five-dimensional vacuum

We investigate, in the context of five-dimensional (5D) Brans-Dicke theory of gravity, the idea that macroscopic matter configurations can be generated from pure vacuum in five dimensions, an approach first proposed in the framework of general relativity. We show that the 5D Brans-Dicke vacuum equations when reduced to four dimensions lead to a modified version of Brans-Dicke theory in four dimensions (4D). As an application of the formalism, we obtain two five-dimensional extensions of four-dimensional O'Hanlon and Tupper vacuum solution and show that they lead two different cosmological scenarios in 4D.Comment: 9 page