endothelial cells, leukocytes and platelets, and their role in the pathophysiology of vaso-occlusion. The clinical manifestations, like anemia, pain crises and multiorgan dysfunction are covered. Factors that modulate disease severity, like the co-inheritance of αthalassemia, gene mutations related to thrombophilia and the elevation of fetal hemoglobin are discussed. Rev. bras. hematol.

In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae), the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae), respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae), all presented significant in vitro inhibition (more active than quinine and chloroquine) of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.Key words: neosergeolide -ellipticine -aspidocarpine -4-nerolidylcatechol -Pothomorphe peltata -Picrolemma spruceiAspidosperma spp.Malaria is the main cause of economic loss and high morbidity in the world today and continues to be endemic to tropical regions such as the Amazon. In the Brazilian Amazon, 1.6 million positive plates (thick smears) in a total of 8 million diagnostic tests for malaria were registered from January 2004 to February 2007 (Ministério da Saúde, Sivep-Malaria 2007). The lack of an effective vaccine and the increasing expansion of strains of Plasmodium falciparum presenting resistance towards commonly used, low-cost antimalarials make control of this disease difficult (Olliaro & Bloland 2001, Wellens & Plowe 2001, Vieira et al. 2001, Gonzales et al. 2003, Alecrim et al. 2006. As a result, the World Health Organization (WHO 1978(WHO , 1995 has been promoting research on natural product based drugs for treatment of disease and many plant species have been evaluated for antimalarial activity (Weniger et al. 2004). In these studies, emphasis has been on the discovery of lead compounds for drug development (Gundidza & Chinyanganya 1999). The rational search for active substances in medicinal plants is a very promising and cost-effective strategy for antimalarial drug discovery. This approach benefits from the accumulated knowledge of the curing capacity of plants possessed by inhabitants of malaria endemic regions and permits the extensive evaluation of natural products derived from these sources (Campbell et al. 1997, 1998, Brandão et al. 1992, 1997, Krettli et al. 2001, Andrade-Neto et al. 2004a.This triage of useful and effective plants is at the heart of traditional medicinal knowledge and is an extremely important source of therapeutic compounds in use today. Important semi-synthetic, low-cost, highly effective antimalarial drugs such as the quinolines (chloroquine, mefloquine, primaquine, etc.) and artemisinin derivatives (sodium artesunate, arteether, artemether, etc.) owe their initial discovery to the isolation and structural identi...

Human parvovirus B19 (B19V) is a small (22-24 nm) nonenveloped DNA virus belonging to the genus Erythrovirus (family Parvoviridae). Although it generally causes self-limiting conditions in healthy people, B19V infection may have a different outcome in patients with inherited hemolytic anemias. In such high-risk individuals, the high-titer replication may result in bone marrow suppression, triggering a life-threatening drop of hemoglobin values (profound anemia, aplastic crisis). To date there is no consensus concerning a B19V screening program either for the blood donations used in the hemotherapy or for high-risk patients. Moreover, questions such as the molecular mechanisms by which B19V produces latency and persistent replication, the primary site (sites) of B19V infection and B19V immunopathology are far from being known. This review summarizes general aspects of B19V molecular characteristics, pathogenesis and diagnostic approaches with a focus on the role of this pathogen in blood transfusions and in patients with some hemoglobinopathies (sickle-cell disease, thalassemia).

The human red blood cell is a biconcave disc of 6-8 × 2 μm that is highly elastic. This capacity to deform enables it to stretch while circulating through narrow capillaries to ensure its main function of gas exchange. Red cell shape and deformability are altered in membrane disorders because of defects in skeletal or membrane proteins affecting protein-protein interactions. Red cell properties are also altered in other pathologies such as sickle cell disease. Sickle cell disease is a genetic hereditary disorder caused by a single point mutation in the β-globin gene generating sickle haemoglobin (HbS). Hypoxia drives HbS polymerisation that is responsible for red cell sickling and reduced deformability. The main clinical features of sickle cell disease are vaso-occlusive crises and haemolytic anaemia. Foetal haemoglobin (HbF) inhibits HbS polymerisation and positively impacts red cell survival in the circulation but the mechanism through which it exerts this action is not fully characterized. In this study, we designed a microfluidic biochip mimicking the dimensions of human capillaries to measure the impact of repeated mechanical stress on the survival of red cells at the single cell scale under controlled pressure. We show that mechanical stress is a critical parameter underlying intravascular haemolysis in sickle cell disease and that high intracellular levels of HbF protect against lysis. The biochip is a promising tool to address red cell deformability in pathological situations and to screen for molecules positively impacting this parameter in order to improve red cell survival in the circulation.

4-nerolidylcatechol (4-NC) is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl) on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast), however 4-NC was more cytotoxic (IC50 = 31.4 µM) and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at −20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at −20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease Background: Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. Objective: To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. Methods: The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. Results: Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. Conclusion: The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients.

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Objective: to understand the phenomenon lived by women in the nursing consultation in gynecological brachytherapy.Method: a qualitative study, with an approach using the Sociological Phenomenology of Alfred Schutz. Thirteen women submitted to brachytherapy treatment participated in two radiotherapy services: one located in Rio de Janeiro and the other in São Paulo, Brazil. The data collection took place between February and November 2012, through a semi-structured interview. Results: two concrete categories emerged: Seeking guidance and Experiencing fear. The experience lived by patients is that people who need guidance, fear the illness and treatment caused by the diagnosis and by the performance of procedures.Conclusion: the nursing consultation for the patient aids the nurse to understand that each patient has a different degree of understanding and that it is effective to personalize this teaching in order to take care of others. Método: estudio cualitativo, con abordaje de Fenomenología Social de Alfred Schutz. Participaron 13 mujeres sometidas a tratamiento por braquiterapia de dos servicios de radioterapia: uno localizado en Rio de Janeiro y otro en San Paulo, Brasil. La recolección ocurrió entre febrero y noviembre de 2012, por medio de entrevista semi-estructurada. DESCRIPTORS:Resultados: surgieron dos categorías concretas de lo vivido: Buscar orientaciones y Vivenciar el miedo. El tipo vivido de las clientes es el de personas que necesitan de orientación, sienten miedo ante la enfermedad y ante el tratamiento, permeados por el diagnóstico y por la realización de los procedimientos.Conclusión: la consulta de enfermería para la cliente subsidia al enfermero a comprender que cada cliente tiene un grado de entendimiento y que se hace vigente personalizar este enseñar para cuidar del otro. DESCRIPTORES:Rol de la enfermera. Atención de enfermería. Neoplasias del cuello uterino. Braquiterapia. Investigación cualitativa.