1,720,965 research outputs found
A HEPCIDIN INHIBITOR MOBILIZES IRON FOR INCORPORATION INTO RED BLOOD CELLS IN AN ADENINE-INDUCED KIDNEY DISEASE MODEL IN RATS
Full text linkAnemia is prevalent in patients with chronic kidney disease (CKD) and is primarily due to a complex interplay of relative erythropoietin deficiency, shortened red blood cell survival and abnormalities in iron homeostasis. A key feature in many patients with anemia of CKD is the limited iron availability for an efficient erythropoiesis despite adequate body iron stores. It is now well established that excess levels of the iron regulatory hormone hepcidin are responsible for downregulating the functional expression of the cellular iron exporter, ferroportin, thereby resulting in a blockade of iron absorption from the diet and iron retention in reticuloendothelial macrophage stores.
Adenine treatment in rats has been proposed as an animal model of anemia of CKD with high hepcidin levels that mirrors the condition in patients.
We developed a adenine-induced renal failure model in rats that simulates the renal failure and anemia condition in patients. We modified the Yokozawa et al. model by giving a diet supplemented with 0.75% adenine for 3 weeks followed by adenine free normal diet for another 3 weeks.
We then tested whether the small molecule bone morphogenetic protein (BMP) inhibitor LDN-193189, which has previously been shown to lower hepcidin levels, was able to mobilize iron into the plasma and improve iron-restricted erythropoiesis in adenine-treated rats.
The modified adenine model had a higher survival rate than previously reported models, while maintaining irreversible renal failure and anemia. We demonstrated that adenine rats had increased hepatic hepcidin mRNA levels, decreased serum iron concentration, increased spleen iron content, low hemoglobin levels and inappropriately low EPO levels relative to the degree of anemia, typical of the clinical condition in patients with anemia of CKD.
LDN-193189 lowered hepatic hepcidin mRNA and mobilized stored iron into plasma in adenine-treated rats. Moreover, the iron was efficiently incorporated into hemoglobin in reticulocytes. However, LDN-193189 alone did not prevent anemia progression in our model.
Lowering hepcidin improved iron availability, but did not improve anemia in an adenine-induced kidney disease model in rats. Co-administration of hepcidin lowering agents with erythropoiesis stimulating agents (ESAs) may be useful as a combination therapy to correct iron balance and thereby reduce the ESA dose needed to achieve target hemoglobin levels
A hepcidin inhibitor mobilizes iron for incorporation into red blood cells in an adenine-induced chronic kidney disease model in rats
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Mutation analysis of hepcidin and ferroportin genes : possible relationship with iron overload in italian prospective blood-donors
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Mutation analysis of hepcidin and ferroportin genes in Italian prospective blood donors with iron overload
No full textMaintenance of iron balance is essential for humans and requires the coordinate regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. Hepcidin, a recently identified antimicrobial peptide produced in the liver, has been shown to play a central role in the homeostatic regulation of iron absorption and distribution [1]. It is a negative regulator of iron absorption in the small intestine and of iron release from macrophages engaged in the recycling of iron senescent erythrocytes [2]. The human hepcidin gene contains three exons that encode a 72-aa precursor (pro-hepcidin) with a characteristic furin cleavage site immediately N-terminal to the 25-aa major hepcidin species found in plasma and urine [3]. Recently, hepcidin has been shown to regulate iron homeostasis by interaction with ferroportin, an iron cellular exporter highly expressed in absorptive enterocytes, macrophages, hepatocytes, and placental cells [4]
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
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