1,720,988 research outputs found

    Modificazioni genetiche in soggetti affetti da Iperparatiroidismo Primario Normocalcemico (NPHPT) e controllo dei valori del paratormone rispetto ad una popolazione sana di riferimento

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    La presentazione clinica dell’iperparatiroidismo primario (o primitivo IPP o pHPT) si è modificata nel tempo passando da una forma plurisintomatica, diagnosticata in pazienti con sintomatologia clinica, ad una forma asintomatica (attualmente la più comune modalità di presentazione di questa patologia), a seguito dell’introduzione del dosaggio automatico della calcemia nella routine ospedaliera e, negli ultimi 10 anni, alla comparsa della forma normocalcemica, conseguente ad una maggiore richiesta di misurare i livelli di paratormone (PTH) nel sangue. L’iperparatiroidismo primario normocalcemico (NPHPT) è stato formalmente riconosciuto per la prima volta nel 2008 nell’ambito di un Workshop sull’IPP asintomatico, ed è caratterizzato da un innalzamento persistente della concentrazione di PTH in associazione a normali livelli di calcio totale e ionizzato, la cui diagnosi è possibile solo dopo aver escluso tutte le cause secondarie di aumento dei valori di PTH sierico. Esistono pochi dati in letteratura sulla epidemiologia del NPHPT e in nessuno dei precedenti studi è stato dosato il Ca2+ oltre alla calcemia totale e sono state escluse, contemporaneamente, tutte le possibili cause di aumento di PTH in presenza di normocalcemia. Per di più, in nessun lavoro finora sono stati misurati i livelli di PTH circolanti con un metodo accurato ed è stata valutata simultaneamente l’importanza relativa dei diversi parametri noti per influenzare la secrezione del PTH in una popolazione di soggetti sani non afferenti a centri per le Malattie Metaboliche Dello Scheletro. In considerazione di ciò, il mio lavoro ha lo scopo di fornire nuovi strumenti sia per la valutazione della prevalenza del NPHPT in una popolazione sana di riferimento sia per la comprensione delle basi genetiche di tale patologia. Inoltre, questo studio mira a valutare l’importanza relativa del Ca2+, del Mg2+, della 25(OH)D e della 1,25(OH)2D nella regolazione della secrezione del PTH in una grande coorte di più di 2.000 volontari sani donatori di sangue. Le analisi biochimiche ematiche sono state effettuate secondo le metodiche attualmente in uso presso il nostro laboratorio. La tipizzazione genotipica dei polimorfismi a singolo nucleotide (SNP) del gene CaSR è avvenuta mediante sequenziamento Sanger tramite un processo di elettroforesi capillare completamente automatizzato. I risultati ottenuti dal sequenziamento degli esoni 2-7 del gene CaSR nei 23 soggetti risultati iperparatiroidei normocalcemici, in particolare quelli relativi agli SNPs situati nell’esone 7d (rs1042636 e rs1801725), sembrano confermare l’ipotesi da noi sostenuta circa l’origine del NPHPT, ovvero che la forma normocalcemica sia la prima fase di un disordine bifasico, il quale successivamente potrebbe manifestarsi come pHPT ipercalcemico. Oltre a ciò, in un paziente NPHPT è stato individuato il polimorfismo rs115230894 (c.1631G>A), situato nel sesto esone del gene CaSR e determinante la variazione aminoacidica non conservativa R544Q, per cui esistono pochi dati in letteratura, non consolidati, circa il suo effetto sul funzionamento della proteina CaSR in pazienti con NPHPT o con IPP. I risultati ottenuti al termine delle analisi biochimiche ematiche sui 2259 soggetti risultati sani dimostrano che, in un ordine gerarchico in condizioni stabili non acute, la 25(OH)D svolge un ruolo significativo nella regolazione della secrezione di PTH rispetto alle altre variabili esaminate, incluso il Ca2+ sierico. È importante sottolineare che questo risultato è rimasto coerente in tre approcci statistici. L’influenza della 25(OH)D può riguardare non solo il suo effetto periferico sull’assorbimento intestinale di calcio, ma anche un suo effetto diretto sulla secrezione di PTH a livello centrale

    Increased proliferation and apoptosis of colonic epithelial cells in dextran sulfate sodium-induced colitis in rats

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    We have evaluated morphologic alterations and epithelial cell apoptosis and proliferation of colonic mucosa in the acute and chronic phases of DSS-induced colitis. Colitis was induced in Sprague-Dawley rats by 7 days of 4% DSS oral administration followed by 7 days of tap water for one, two, and three cycles. Control rats receved tap water only. Morphological changes in colonic mucosa were evaluated and scored by light and scanning electron microscopy. Apoptosis was studied by TUNEL assay and cell proliferation by Ki-67 immunoreaction. The expression of both proapoptotic (Fas, FasL, Bax, p53) and antiapoptotic (Bcl2) cellular proteins was determined by immunohistochemistry. Morphologic assessment showed the most severe colonic epithelial lesions and inflammation in the distal colon with a trend to increasing severity from the first to the third DSS cycle. In DSS rats, the epithelial apoptotic index increased 20-fold after the first cycle and 120-fold after the second and third cycles compared with the controls; in the same way, the expression index of proapoptotic proteins (Fas, FasL, Bax, p53) dramatically increased. The proliferative index increased about 40 to 60-fold compared to controls, with no difference among the three DSS cycles. In conclusion, DSS-induced colitis in rats, which has many structural and ultrastructural features similar to those seen in human ulcerative colitis, is a suitable model for studying increased epithelial apoptosis and proliferation. Further studies employing this model will permitt two hypotheses to be tested. (1) Increased apoptosis may lead to a breakdown of the epithelial barrier function and facilitate the mucosal invasion of intraluminal microorganisms and/or antigens. (2) Abnormal and persistent epithelial hyperproliferation could be causally related to the development of colorectal cancers in the setting of chronic colonic inflammation

    Peyer's patches epithelium in the rat - A morphological, immunohistochemical, and morphometrical study

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    The epithelial layer covering lymphoid follicles of Peyer's patches consists of cells with a different surface morphology. Some of these cells have been described as a distinct cytotype, the so-called M cells. In order to resolve the controversy on the specific morphological and biochemical markers of M cells, structural, ultrastructural, and morphometrical study of the epithelium covering the rat Peyer's patches were performed. Peyer's patches from healthy rats were processed for light microscopy, immunohistochemistry, in situ nick-end labeling (TUNEL), and scanning and transmission electron microscopy. A morphometric study was also performed to evaluate microvillus density, length, and number of lysosomes in different areas of the epithelium. Peyer's patches were covered by simple columnar/cubical dome epithelium (DE). Scarce goblet cells and a large number of enterocytes were observed. Ultrastructural observations revealed that the DE showed cells with different morphology. The density and length of microvilli and the lysosome number varied along the whole dome without significant differences. The DE cells characterized by short and disorganized microvilli appeared always in close spatial relationship with lymphocytes. In conclusion, the concept that distinct cell types (enterocytes and M cells) can be identified in the rat DE does not appear to be valid based on morphological criteria. It seems correct to consider that in rat Peyer's patches the presence of scarce goblet cells and a large number of enterocytes showing dynamic morphofunctional modifications is related to the functional state and/or to cell cycle

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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