1,721,021 research outputs found
MOLECULAR AND CELLULAR MECHANISMS OF VASCULAR CALCIFICATION: PATHOGENESIS AND TREATMENT
Full text linkVascular calcification is a significant contributor to cardiovascular risk in chronic kidney disease (CKD) patients, and its extent and severity has been correlated with mortality in several studies.
Hyperphosphatemia predisposes these patients to early and progressive vascular calcification: it appears to be involved in a number of mechanisms that trigger and promote the progression of this active and cell-mediated pathological process, in which vascular smooth muscle cells (VSMCs) residing in the tunica media of blood vessels are the main cell type actively involved.
We developed an in vitro model to elucidate the molecular and cellular mechanisms involved in the pathogenesis of vascular calcification: in particular, we challenged rat VSMCs for 7-15 days with high Pi (inorganic phosphorous) with the purpose to reproduce in vitro the same pathological process that occurs in CKD patients in vivo. We investigated the high Pi-induced calcium deposition and the modulation of different cellular biological processes (apoptosis, autophagy and VSMC osteoblastic differentiation) through molecular biology, proteomic and immunohistochemistry analysis.
First of all, we studied the modulation of osteonectin (SPARC), a major non collagenous protein of bone matrix that is associated, generally, with remodeling of tissues, mineralization and pathological responses to injury. Since there are controversial results regarding its role during the process of vascular calcification, we investigated osteonectin expression both in vitro and ex-vivo, and the results suggest a pro-calcifying role of this protein in the process of vascular calcification.
Then, we developed an experimental strategy to delay the progression of calcium deposition in our in vitro model. We studied the potential effect of repeated and short time suspension of high Pi treatment (process that we called “Wash Out”) on the progression of calcium deposition, trying to reproduce the same temporal decrease of Pi levels that occurs in CKD patients treated with haemodialysis. Surprisingly, we discovered that it is sufficient a temporary total absence or partial decrease in Pi concentration under a so called “trigger threshold” during the process of calcification to obtain a substantial inhibition of calcium deposition. The molecular and cellular pathways involved in this protective action are apoptosis, VSMC osteoblastic differentiation and autophagy: the formers are partially inhibited, while the latter is incremented after the “Wash Out” treatment.
Finally, we investigated the mechanism of action of two drugs CKD patients are treated with in the attempt to reduce hyperphosphatemia and to contrast secondary hyperparathyroidism, respectively: Lanthanum Chloride (LaCl3) and Calindol. We demonstrated that these compounds significantly delay the progression of high Pi-induced VSMC calcium deposition, but with different mechanisms of action: both of them delay VSMC osteoblastic transformation, and, in particular, lanthanum chloride preserves VSMC lineage markers expression and partially prevents VSMC apoptosis, whereas calindol increases the expression of an anti-calcifying protein.
These in vitro discoveries can suggest that vascular calcification is a multifactorial process that involves different cellular and molecular pathways, and that it is of relevant importance to control as more as possible phosphate levels in CKD patients, even with diet, because high-Pi is the most dangerous key regulator of vascular calcification in end stage renal disease pathology
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
Secondary Hyperparathyroidism in End-Stage Renal Disease : No Longer a Matter for Surgeons?
No full textHyperphosphatemia, hypocalcemia and vitamin D deficiency are the main factors involved in the pathogenesis of secondary hyperparathyroidism (SHPT). Moreover, the skeletal resistance to parathyroid hormone is not only a high-turnover bone accompanying SHPT, but may also play a crucial role in the onset of low-turnover bone disease in uremia. However, a growing body of evidence suggests that other hormones play a key role in this disease, such as fibroblast growth factor 23, Klotho and sclerostin. SHPT causes both bone-associated and non-skeletal consequences, including cardiovascular calcifications. Furthermore, vitamin D and calcium (Ca)-containing phosphate binders may increase Ca load. Anyway, the rate of parathyroidectomy in end-stage renal disease has greatly decreased during the last decade. Is there any room left for surgeons?
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Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Le alterazioni metaboliche del paziente nefropatico
No full textNei soggetti sani, i reni regolano l’omeostasidel calcio e del fosforo attraverso il meccanismo di riassorbimento e secrezione tubulare.
Nei pazienti affetti da patologia renale cronica (CKD, Chronic Kidney Disease), il mantenimento omeostatico risulta essere seriamente compromesso, causando una serie di alterazioni metaboliche importanti.
L’alterazione della funzionalità renale si ripercuote sul metabolismo osseo, quindi, si parla di osteodistrofia renale: le numerose variazioni biochimiche nei livelli di Ca, P, vitamina D, PTH (Parathyroid Hormone), fattore di crescita dei fibroblasti-23 (FGF-23,
Fibroblastic Growth Factor-23), i cambiamenti nella morfologia, nel volume, nel turnover e
nella mineralizzazione delle ossa, le calcificazioni vascolari e di altri tessuti molli vengono
inclusi sotto la definizione di “Chronic Kidney
Disease Mineral and Bone Disorders” (CKD-
MBD), disordine sistemico del metabolismo
minerale.
Nonostante le prime manifestazioni cliniche del CKD-MBD siano legate ad alterazioni di laboratorio (iperfosforemia, deficit di vitamina
D, iperparatiroidismo secondario – SHPT, Secondary Hyperparathyroidism –, ipocalcemia)e a fratture ossee, la più grave complicanza rimane l’insorgenza delle calcificazioni vascolari, che sono presenti nel 69% dei pazienti in
dialisi e che causano elevata morbidità e mortalità.
Risulta, quindi, necessario adottare strategie terapeutiche: agenti farmacologici relativamente nuovi come sevelamer, analoghi del calcitriolo e calciomimetici possono essere somministrati singolarmente o in combinazione
per cercare di minimizzare le complicanze associate ad iperfosfatemia e a SHPT
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