Rapid diagnostic tests for malaria: past, present and future

Prompt and accurate diagnosis of malaria is part of an effective disease management (1) , because if not treated malaria can quickly become life-threatening, whereas false positives increase treatment costs and drug-induced resistance, giving a wrong idea of therapeutic efficacy. Since the symptoms of malaria are nonspecific, the observation of clinical features alone might not be enough and should be confirmed with a parasitological analysis. Microscopic examination of Giemsa-stained thin and/or thick blood smears remains the conventional approach for diagnosis (2). The sensitivity of this relatively inexpensive method is excellent, allowing the detection of as few as 5 parasites per µL of blood, and permitting also the determination of the infecting species and of the developmental stage of circulating parasites. In addition, smears provide a permanent record for quality assessment of the diagnosis. However, microscopy requires considerable expertise learned through extended training, the procedure is labor-intensive and time-consuming, and the variability in stains and in techniques used to collect and process blood affects slide interpretation (3). Finally, routine clinical microscopy cannot reliably detect very low parasitemias (<5 parasites/µL) or sequestered parasites, and mixed infections are often missed, especially when Plasmodium malariae and Plasmodium ovale are present, as their densities are often low relative to Plasmodium falciparum

Understanding hemicellulose-cellulose interactions in cellulose nanofibril-based composites

Plant-based polysaccharides (cellulose and hemicellulose) are a very interesting option for the preparation of sustainable composite materials to replace fossil plastics, but the optimum bonding mechanism between the hard and soft components is still not well known. In this work, composite films made of cellulose nanofibrils (CNF) and various modified and unmodified polysaccharides (galactoglucomannan, GGM; hydrolyzed and oxidized guar gum, GGhydHox; and guar gum grafted with polyethylene glycol, GG-g-PEG) were characterized from the nano- to macroscopic level to better understand how the interactions between the composite components at nano/microscale affect macroscopic mechanical properties, like toughness and strength. All the polysaccharides studied adsorbed well on CNF, although with different adsorption rates, as measured by quartz crystal microbalance with dissipation monitoring (QCM-D). Direct surface and friction force experiments using the colloidal probe technique revealed that the adsorbed polysaccharides provided repulsive forces–well described by a polyelectrolyte brush model – and a moderate reduction in friction between cellulose surfaces, which may prevent CNF aggregates during composite formation and, consequently, enhance the strength of dry films. High affinity for cellulose and moderate hydration were found to be important requirements for polysaccharides to improve the mechanical properties of CNF-based composites in wet conditions. The results of this work provide fundamental information on hemicellulose-cellulose interactions and can support the development of polysaccharide-based materials for different packaging and medical applications.Peer reviewe

Micelle carriers based on dendritic macromolecules containing bis-MPA and glycine for antimalarial drug delivery

Biomaterials for antimalarial drug transport still need to be investigated in order to attain nanocarriers that can tackle essential issues related to malaria treatment, e.g. complying with size requirements and targeting specificity for their entry into Plasmodium-infected red blood cells (pRBCs), and limiting premature drug elimination or drug resistance evolution. Two types of dendritic macromolecule that can form vehicles suitable for antimalarial drug transport are herein explored. A new hybrid dendritic-linear-dendritic block copolymer based on Pluronic\xC2\xAE F127 and amino terminated 2,2'-bis(glycyloxymethyl)propionic acid dendrons with a poly(ester amide) skeleton (HDLDBC-bGMPA) and an amino terminated dendronized hyperbranched polymer with a polyester skeleton derived from 2,2'-bis(hydroxymethyl)propionic acid (DHP-bMPA) have provided self-assembled and unimolecular micelles. Both types of micelle carrier are biocompatible and exhibit appropriate sizes to enter into pRBCs. Targeting studies have revealed different behaviors for each nanocarrier that may open new perspectives for antimalarial therapeutic approaches. Whereas DHP-bMPA exhibits a clear targeting specificity for pRBCs, HDLDBC-bGMPA is incorporated by all erythrocytes. It has also been observed that DHP-bMPA and HDLDBC-bGMPA incorporate into human umbilical vein endothelial cells with different subcellular localization, i.e. cytosolic and nuclear, respectively. Drug loading capacity and encapsulation efficiencies for the antimalarial compounds chloroquine, primaquine and quinacrine ranging from 30% to 60% have been determined for both carriers. The resulting drug-loaded nanocarriers have been tested for their capacity to inhibit Plasmodium growth in in vitro and in vivo assays

Sistema de Información Clínica para el desarrollo de Centros de Salud periféricos

La manipulación de los datos clínicos es de gran importancia para la obtención de información relevante en la administración y gestión de instituciones de salud. Asimismo, el volumen de datos generados y la necesidad de su procesamiento en tiempo real, hacen necesaria la utilización de herramientas informáticas para obtener una solución que satisfaga todos los requerimientos. Sin embargo, la complejidad de la estructura organizacional de las instituciones sanitarias dificulta la adaptación de un sistema informático sin efectuar previamente un análisis y rediseño profundo, haciendo necesaria la cooperación y participación de todas las partes involucradas. En el presente trabajo se exponen las etapas de análisis de dominio y diseño de una herramienta que será implementada en un Hospital Público de la Provincia de San Juan. Para esto se realizó un estudio de los procesos de negocio del Centro de Salud, como así también de las formas de optimización de estos procedimientos. El diseño de la aplicación se concretó siguiendo una metodología de desarrollo basada en UML y, actualmente, su programación está siendo realizada utilizando el lenguaje de programación Java, sobre un servidor JBoss versión 5.1.0 y con un motor de Base de Datos MySQL versión 5.1.37.Sociedad Argentina de Informática e Investigación Operativ

Sistema de información clínica para el desarrollo de centros de salud periféricos

La manipulación de los datos clínicos es de gran importancia para la obtención de información relevante en la administración y gestión de instituciones de salud. Asimismo, el volumen de datos generados y la necesidad de su procesamiento en tiempo real, hacen necesaria la utilización de herramientas informáticas para obtener una solución que satisfaga todos los requerimientos. Sin embargo, la complejidad de la estructura organizacional de las instituciones sanitarias dificulta la adaptación de un sistema informático sin efectuar previamente un análisis y rediseño profundo, haciendo necesaria la cooperación y participación de todas las partes involucradas. En el presente trabajo se exponen las etapas de análisis de dominio y diseño de una herramienta que será implementada en un Hospital Público de la Provincia de San Juan. Para esto se realizó un estudio de los procesos de negocio del Centro de Salud, como así también de las formas de optimización de estos procedimientos. El diseño de la aplicación se concretó siguiendo una metodología de desarrollo basada en UML y, actualmente, su programación está siendo realizada utilizando el lenguaje de programación Java , sobre un servidor JBoss versión 5.1.0 y con un motor de Base de Datos MySQL versión 5.1.37.Sociedad Argentina de Informática e Investigación Operativ

Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery.

The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems

Caracterización geoquímica de las sales procedentes de deyecciones de palomas en patrimonio monumental. Iglesia de El Salvador (Úbeda, Jaén)

El deterioro ocasionado en el patrimonio histórico a consecuencia de las sales procedentes de deyecciones de palomas debe ser adecuadamente identificado y localizado. La realización de mapas de conductividad superficial en los paramentos, la extracción de sales mediante apósitos de celulosa y su análisis químico, y la posterior evaluación geoquímica constituyen la mejor combinación metodológica disponible para identificar la procedencia de este tipo de sales. A partir de un caso práctico se ha podido concluir que, en las zonas donde son patentes estas concentraciones salinas y sus consecuencias, predominan las sales de KNO3, pero donde los precipitados están en una fase incipiente de acumulación, es posible identificar dicho proceso activo por el predominio de Na+, K+, NO3- y Cl- en las extracciones salinas obtenidas mediante apósitos de celulosa. La correcta identificación del origen de las sales en los paramentos permite diseñar de forma eficiente las actuaciones de limpieza y mantenimiento

Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery

The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems

Possible roles of amyloids in malaria pathophysiology

The main therapeutic and prophylactic tools against malaria have been locked for more than a century in the classical approaches of using drugs targeting metabolic processes of the causing agent, the protist Plasmodium spp., and of designing vaccines against chosen antigens found on the parasite's surface. Given the extraordinary resources exhibited by Plasmodium to escape these traditional strategies, which have not been able to free humankind from the scourge of malaria despite much effort invested in them, new concepts have to be explored in order to advance toward eradication of the disease. In this context, amyloid-forming proteins and peptides found in the proteome of the pathogen should perhaps cease being regarded as mere anomalous molecules. Their likely functionality in the pathophysiology of Plasmodium calls for attention being paid to them as a possible Achilles' heel of malaria. Here we will give an overview of Plasmodium-encoded amyloid-forming polypeptides as potential therapeutic targets and toxic elements, particularly in relation to cerebral malaria and the blood-brain barrier function. We will also discuss the recent finding that the genome of the parasite contains an astonishingly high proportion of prionogenic domains

Synthesis of an Azide- and Tetrazine-Functionalized [60]Fullerene and Its Controlled Decoration with Biomolecules

Bingel cyclopropanation between Buckminster fullerene and a heteroarmed malonate was utilized to produce a hexakis-functionalized C60 core, with azide and tetrazine units. This orthogonally bifunctional C60 scaffold can be selectively one-pot functionalized by two pericyclic click reactions, that is, inverse electron-demand Diels-Alder and azide-alkyne cycloaddition, which with appropriate ligands (monosaccharides, a peptide and oligonucleotides tested) allows one to control the assembly of heteroantennary bioconjugates.</p