Adherence to human lung microvascular endothelial cells (HMVEC-L) of Plasmodium vivax isolates from Colombia

ABSTARCT: For years Plasmodium vivax has been considered the cause of benign malaria. Nevertheless, it has been observed that this parasite can produce a severe disease comparable to Plasmodium falciparum. It has been suggested that some physiopathogenic processes might be shared by these two species, such as cytoadherence. Recently, it has been demonstrated that P. vivax-infected erythrocytes (Pv-iEs) have the capacity to adhere to endothelial cells, in which intercellular adhesion molecule-1 (ICAM-1) seems to be involved in this process

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Translating chitosan to clinical delivery of nucleic acid-based drugs

A number of systems based on synthetic molecules, among them cationic liposomes and poly(ethylene imine)-based polymers, have been proposed as delivery vehicles for nucleic acids. Some of these systems have even reached the market, ensuring efficient and transient transfection levels in a variety of cell types. However, toxicity issues have limited their application in vivo. In this context, chitosan, a biocompatible and biodegradable polysaccharide, has been proposed as a promising alternative for the delivery of nucleic acid-based molecules. Here we present an overview of the state of the art of chitosan-based vectors for nucleic acid delivery and the most recent data on the in vivo testing of the proposed systems. We additionally express our view on the barriers that might be hampering the translation of this knowledge into clinical practice and the challenges that need to be fulfilled for these promising vehicles to reach patients.The Programa Operacional Factores de Competitividade — COMPETE and the Portuguese funds through FCT— Fundação para a Ciência e a Tecnologia (PTDC/CTM-NAN/115124/2009 and PEst C/SAU/LA0002/2011) that supported this work. C.P.G. and C.D.F.L. acknowledge FCT for their PhD scholarships (SFRH/BD/79930/2011 and SFRH/BD/77933/2011). P.M.D.M. is supported by a Marie Curie Actions grant within the framework of the European Union’s Seventh Framework Program (PIEF-GA-2011–300485). The authors would like to thank A. Nunes (IBMC-INEB) for her contribution to the graphic design of Figure 2

On cytoadhesion of Plasmodium vivax: raison d'être?

It is generally accepted that Plasmodium vivax, the most widely distributed human malaria parasite, causes mild disease and that this species does not sequester in the deep capillaries of internal organs. Recent evidence, however, has demonstrated that there is severe disease, sometimes resulting in death, exclusively associated with P. vivax and that P. vivax-infected reticulocytes are able to cytoadhere in vitro to different endothelial cells and placental cryosections. Here, we review the scarce and preliminary data on cytoadherence in P. vivax, reinforcing the importance of this phenomenon in this species and highlighting the avenues that it opens for our understanding of the pathology of this neglected human malaria parasite.798

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

<p>Abstract</p> <p>Background</p> <p>To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. <it>Caesalpinia pluviosa</it>, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity.</p> <p>Methods</p> <p>Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested <it>in vitro </it>against chloroquine-sensitive (3D7) and -resistant (S20) strains of <it>Plasmodium falciparum</it> and <it>in vivo </it>in <it>Plasmodium chabaudi</it>-infected mice. <it>In vitro </it>interaction with artesunate and the active <it>C. pluviosa </it>fractions was assessed, and mass spectrometry analyses were conducted.</p> <p>Results</p> <p>At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to <it>m/z </it>303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of <it>m/z </it>137 and 153.</p> <p>Conclusions</p> <p>The findings show that the F4 fraction of <it>C. pluviosa </it>exhibits anti-malarial activity <it>in vitro </it>at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained <it>in vivo </it>after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.</p

Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type

Background:Although salt intake is considered a probable risk factor for gastric cancer, relevant studies have provided heterogeneous results, and the magnitude of the association has not been accurately quantified.Methods:To quantify gastric cancer risk in relation to dietary salt exposure according to Helicobacter pylori infection status and virulence, smoking, tumour site, and histological type, we evaluated 422 gastric cancer cases and 649 community controls. Salt exposure was estimated in the year before the onset of symptoms through: sodium intake (estimated by a food frequency questionnaire (FFQ)); main food items/groups contributing to dietary sodium intake; visual analogical scale for salt intake preference; use of table salt; and duration of refrigerator ownership.Results:Comparing subjects with the highest with those with the lowest salt exposure (3rd vs 1st third), sodium intake (OR2.01, 95% CI: 1.16-3.46), consumption of food items with high contribution to sodium intake (OR2.54, 95% CI: 1.56-4.14) and salt intake evaluated by visual analogical scale (OR1.83, 95% CI: 1.28-2.63) were associated with an increased gastric cancer risk. Subjects owning a refrigerator for 50 years had a lower risk for gastric cancer (OR0.28, 95% CI: 0.14-0.57). These associations were observed regardless of H. pylori infection status and virulence, smoking, tumour site or histological type.Conclusion:Our results support the view that salt intake is an important dietary risk factor for gastric cancer, and confirms the evidence of no differences in risk according to H. pylori infection and virulence, smoking, tumour site and histological type. © 2011 Cancer Research UK All rights reserved.This work was performed using grants from Fundac¸ão para a Ciência e a Tecnologia (POCTI/SAU-ESP/56126/2004, POCTI/ SAU-ESP/61685/2004, PTDC/SAU-ESA/71517/2006) and Agência Portuguesa de Seguranc¸a Alimentar. This work, presented at the GRELL Meeting 2010 in Toledo, was awarded the ‘Enrico Anglesio’ Prize, offered by the ‘Anglesio Moroni Foundation’, Turin, Italy

Anti-inflammatory effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) Plumel

<p>Abstract</p> <p>Background</p> <p>The species <it>Himatanthus drasticus </it>is popularly known in Northeast Brazil as "janaguba" and belongs to the family Apocynaceae. The latex collected from its stem bark is used for several purposes including anti-inflammatory properties and presents among its bioactive constituents the pentacyclic triterpene lupeol. The objective of the present work was to study <it>in vivo </it>and <it>in vitro </it>the lupeol acetate (LA) isolated from the plant latex, in several models of inflammation.</p> <p>Methods</p> <p>Male Swiss mice (25-30 g, 6-24 animals per group) were administered with LA, 30 min before the test initiation. In the evaluation of analgesic activity the formalin test was used. The anti-inflammatory activity was evaluated by the following tests: paw edema induced by carrageenan and dextran, and the carrageenan-induced neutrophil migration into peritoneal cavities. Furthermore, the effect of LA on the myeloperoxidase release (MPO, an inflammation biomarker) from human neutrophils was also determined, as well as its antioxidant potential by the DPPH assay.</p> <p>Results</p> <p>In the formalin test, LA (10, 25 and 50 mg/kg, i.p.) inhibited both the 1^st(neurogenic, 0-5 min) and mainly the 2^nd(inflammatory, 20-25 min) phase. Naloxone completely reversed the LA effect, indicating the participation of the opioid system. LA also significantly inhibited carrageenan- and dextran-induced paw edemas, as well as the neutrophil migration to the peritoneal cavity evaluated by the carrageenan-induced pleurisia. In this model, the effect of a very low dose of LA (0.1 mg/kg) was potentiated by the same dose of pentoxifylline (PTX), a known TNF-alpha inhibitor. LA (25 and 50 μg/ml) was also very effective in inhibiting MPO released from stimulated human neutrophils, and significantly decreased the number of cells expressing iNOS activity in the paw of mice submitted to carrageenan-induced edema, suggesting a drug involvement with the NO system.</p> <p>Conclusions</p> <p>The anti-inflammatory effect of LA probably involves the opioid system, as indicated by the complete blockade of the opioid antagonist naloxone. Furthermore, the LA effect was potentiated by PTX (a TNF-alpha inhibitor). LA also decreased the number of iNOS cells, suggesting the participation of pro-inflammatory cytokines and the NO system in the drug action.</p

Nernst branes in gauged supergravity

We study static black brane solutions in the context of N = 2 U(1) gauged supergravity in four dimensions. Using the formalism of first-order flow equations, we construct novel extremal black brane solutions including examples of Nernst branes, i.e. extremal black brane solutions with vanishing entropy density. We also discuss a class of non-extremal generalizations which is captured by the first-order formalism.Comment: 44 pages, 3 figures, v2: added appendix B and references, minor typographic changes, v3: added some clarifying remarks, version published in JHE

Holomorphic variables in magnetized brane models with continuous Wilson lines

We analyze the action of the target-space modular group in toroidal type IIB orientifold compactifications with magnetized D-branes and continuous Wilson lines. The transformation of matter fields agree with that of twisted fields in heterotic compactifications, constituting a check of type I/heterotic duality. We identify the holomorphic N = 1 variables for these compactifications. Matter fields and closed string moduli are both redefined by open string moduli. The redefinition of matter fields can be read directly from the perturbative Yukawa couplings, whereas closed string moduli redefinitions are obtained from D-brane instanton superpotential couplings. The resulting expressions reproduce and generalize, in the presence of internal magnetic fields, previous results in the literature.Comment: 9 pages, no figures; v2: conventions for Wilson lines changed, major simplifications in expressions, discussions extended, typos corrected, some references adde