Anti-malarial effect of gum arabic

<p>Abstract</p> <p>Background</p> <p>Gum Arabic (GA), a nonabsorbable nutrient from the exudate of <it>Acacia senegal</it>, exerts a powerful immunomodulatory effect on dendritic cells, antigen-presenting cells involved in the initiation of both innate and adaptive immunity. On the other hand GA degradation delivers short chain fatty acids, which in turn have been shown to foster the expression of foetal haemoglobin in erythrocytes. Increased levels of erythrocyte foetal haemoglobin are known to impede the intraerythrocytic growth of <it>Plasmodium </it>and thus confer some protection against malaria. The present study tested whether gum arabic may influence the clinical course of malaria.</p> <p>Methods</p> <p>Human erythrocytes were <it>in vitro </it>infected with <it>Plasmodium falciparum </it>in the absence and presence of butyrate and mice were <it>in vivo </it>infected with <it>Plasmodium berghei </it>ANKA by injecting parasitized murine erythrocytes (1 × 10⁶) intraperitoneally. Half of the mice received gum arabic (10% in drinking water starting 10 days before the day of infection).</p> <p>Results</p> <p>According to the <it>in vitro </it>experiments butyrate significantly blunted parasitaemia only at concentrations much higher (3 mM) than those encountered <it>in vivo </it>following GA ingestion (<1 μM). According to the <it>in vivo </it>experiments the administration of gum arabic slightly but significantly decreased the parasitaemia and significantly extended the life span of infected mice.</p> <p>Discussion</p> <p>GA moderately influences the parasitaemia and survival of <it>Plasmodium-</it>infected mice. The underlying mechanism remained, however, elusive.</p> <p>Conclusions</p> <p>Gum arabic favourably influences the course of murine malaria.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Programmed cell death of iron-deficient and lead exposed erythrocytes

Eisenmangelanämie und Bleiintoxikation verstärken die Empfindlichkeit der Erythrozyten für stressinduzierte Apoptose. Dieser Effekt ist nicht zuletzt auf die verstärkte Aktivität des Ca2+-abhängigen Kationenkanals zurückzuführen. Die zelluläre Zunahme des intrazellulären Ca2+ durch Aktivierung dieses Kanals wiederum aktiviert die Scramblase. Dies zieht nun unmittelbar die Präsentation von Phosphatidylserin auf der äußeren Zellmembran und die Aktivierung des GARDOS-Kanals mit einem anschließenden Verlust von KCl und die konsekutive Schrumpfung der Zelle nach sich. Die bereits beschriebenen Mechanismen können für das beschleunigte Recycling der Erythrozyten im Kreislauf verantwortlich sein und möglicherweise die Symptome der Blei-induzierten Anämie, sowie der Eisenmangelanämie erklären. Die Studie eröffnet somit neue Aspekte bezüglich der pathophysiologischen Ursachen für eine Anämie. Ferner entstehen hieraus Ideen für neue Behandlungsansätze. Dazu gehören potentielle Hemmstoffe der erythrozytären Apoptose als Medikamente gegen verschiedene Anämieformen. Durch ihre Anwendung wäre das Ausmaß der Symptomkomplikationen möglicherweise geringer und die Indikationsstellung für eine Blut-Transfusion möglicherweise dehnbar. Die Prognose der chronischen Herzinsuffizienz wird beispielsweise durch eine Anämie entscheidend verschlechtert und verbessert sich durch deren adäquate Behandlung. Ein medikamentöses Eingreifen wäre durch das detaillierte Wissen über die pathophysiologischen Entstehungsmechanismen der Anämie erheblich erleichtert.Recapitulatory it is to say that both, iron-deficiency causing anemia and lead-intoxication, enhance the sensibility of erythrocytes to run into stress induced apoptosis. This effect isn´t only caused by the increased activity of a calcium dependant cation channel. The gain of intracellular Ca2+ by this mechanism again activates an enzyme called scramblase, which is proximately causing phosphatidylserine-exposure on the outer cell membrane and activation of the GARDOS-channel with consecutive loss of intracellular potassium-chloride inducing cell shrinkage. Erythrocytes exposing phosphatidylserine are recognized, bound, engulfed and degraded by macrophages. According to this red blood cells can be filtered of the circulating blood. These pathways are possibly responsible for the accelerated recycling of erythrocytes in circulation and therefore provide an explanation of the symptoms of the mentioned forms of anemia. This study opens some new aspects of pathophysiologic reasons of anemia. It also develops novel ideas of individual treatment, e. g. potential inhibitors of erythrocyte apoptosis. By application of these medications complications of severe forms of anemia could eventually be alleviated and patients would need fewer blood transfusions. The prognosis of chronic heart disease is decisively influenced by anemic conditions and could be improved by adequate treatment. Drug intervention would strongly be eased by detailed knowledge about concrete mechanisms of erythrocyte apoptosis and its connection with anemia

Cl- channel blockers NPPB and niflumic acid blunt Ca(2+)-induced erythrocyte 'apoptosis'.

Exposure to Ca2+ ionophore ionomycin, osmotic shock, oxidative stress and glucose depletion trigger cell shrinkage and scramblase-mediated phosphatidylserine exposure at the outer leaflet of the erythrocyte cell membrane. The effects are partially due to activation of GARDOS channels and subsequent cellular K+ loss leading not only to cell shrinkage but also participating in the triggering of erythrocyte scramblase. As conductive loss of K+ would depend on the parallel loss of anions we hypothesised that activation of scramblase is similarly dependent on the activity of Cl- channels. To test this hypothesis, we used Cl- channel blockers NPPB and niflumic acid. It is shown here that treatment of erythrocytes with 1 microM ionomycin leads to cellular K+ loss, decrease of hematocrit and decrease of forward scatter in FACS analysis reflecting cell shrinkage as well as increase of annexin positive cells reflecting phosphatidylserine exposure. Those events were significantly blunted in the presence of 100 microM NPPB by 34% (K+ loss), 45% (hematocrit), 32% (forward scatter) and 69% (annexin binding), or in the presence of 100 microM niflumic acid by 15% (forward scatter) and 45% (annexin binding), respectively. Moreover, oxidative stress triggered annexin binding which was again significantly inhibited (by 51%) in the presence of 100 microM NPPB. In conclusion, Cl- channels presumably participate in the regulation of erythrocyte 'apoptosis'