1,721,036 research outputs found
Effect of dihydroartemisinin on human Erythroid cell differentiation
No full textWomen in their first pregnancy are at the very high-risk of developing severe malaria which includes maternal anemia, low birth weight of newborns and increased mortality of both mother and infants. The WHO recommends the Intermittent Preventive Treatment to cure malaria during gestation, but drug safety in pregnancy is an issue.
Artemisinin combination therapy is the first line treatment for uncomplicated malaria, but artemisinin derivatives carry a potential toxic effect on embryos. In animal studies they affect embryonic erythroid precursors only on certain days of gestation. This suggests that the target of DHA toxicity could be the primitive erythropoiesis. Our aim was to study the effect of artemisinin and 4-aminoquinoline derivatives on in vitro models which reproduce human erythropoiesis: K562 leukemia cells and CD34+ from human peripheral blood. Cells switch from fetal and embryonic to adult hemoglobin in presence of hemin or butyric acid (K562) or erythropoietin (CD34+). We found that artemisinins inhibit both cell growth and erythroid differentiation (P<0.05), measured as adult hemoglobin synthesis and erythroblasts count. The effect is dose and time-dependent. DHA, which is the active metabolite of artemisinins, has the strongest effect. As expected chloroquine and amodiaquine did not affect cell differentiation, confirming the suitability of the models for studying drug toxicity on developmental erythropoiesis. Moreover, as in animal studies, our results show that a toxic effect of DHA could occur if administered during first trimester of pregnancy, when fetal blood consists mostly of primitive erythroblasts. The support of EU Antimal Project 18834 is acknowledge
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Effect of dihydroartemisinin of human erythroid cell differentiation : implications for malaria treatment in pregnancy
No full textBACKGROUND: Severe malaria in pregnancy causes maternal anemia, low birth weight increased mortality of both mother and infants. WHO recommends few antimalarials due to safety problems. Artemisinin combination therapy is the first line treatment, however artemisinin derivatives showed animal embryotoxicity with a reduction of embryonic erythrocytes when treatment is performed on certain days of gestation. AIMS: To investigate the effect of Dihydroartemisinin (DHA), the metabolite of artemisinins, on an in vitro model reproducing human erythropoiesis and to characterize the erythroid target stage, in order to predict the window of susceptibility to DHA in human pregnancy. METHODS: The mononuclear cells derived from pheripheral blood of healthy volunteers were enriched for CD34+ cells by positive selection using anti-CD34-tagged magnetic beads. CD34+ cells were cultured for 14 days with a specific medium containing erythropoietin to induce erythroid differentiation. DHA at 0,5 or 2 ÂμM, according to the dosages of previous animal experiments, was added for the first time at day 0 (on isolated stem cell), at day 2 (on early erythroid progenitors), at day 4 (in presence of both early progenitors and pro-erythroblasts), at day 7 (on basophilic erythroblasts) or at day 11 (polychromatic erythroblasts) then continuously every 3 days up to 14 days, because of its short half life. Cells growth and viability were evaluated by trypan blue exclusion; erythroid differentiation was investigated by cytofluorimetric analysis of Glycophorin A (GPA) expression, by morphological analysis on benzidine-May-Grunwald-Giemsa stained smears and by erythroid specific gene expression analysis with real-time PCR. RESULTS: DHA was added on stem cells or early erythroid progenitors caused a transient inhibition of both cell growth and differentiation up to day 7, but then the treated cells started growing and completed their erythroid differentiation at day 14 of culture. When DHA was added on basophilic erythroblasts, a significant and long lasting effect decrease in proliferation as well as a delay in erythroid differentiation was observed. Up to day 14. DHA added on mature stages i.e. polychromatic erythroblasts, only a small reduction of cell growth has been observed without any consequence for the erythroid cell differentiation. CONCLUSIONS: These data suggest that DHAâ s specific target is the basophilic erythroblast, since DHA added at this stage causes a significant inhibition of erythroid differentiation. Based on these in vitro results, we hypothesize that DHA could affect human primitive erythropoiesis, which occurs during the late phase of human secondary yolk sac erythropoiesis (weeks 4-8 of gestation), when foetal blood is formed of only primitive erythroblasts. This means that if the treatment with DHA or artemisinin derivatives is performed during the first trimester of human pregnancy, toxic effects on embryo could be expected
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