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the effects of GLP-1 on SIRT1 and on the related metabolic pathways in vascular endothelial cells: potential effects on vascular injury in diabetic patients
No full textBackground: Incretin therapy may have a potential protective role in the treatment of diabetes associated with the cardiovascular comorbidities. GLP-1 may have beneficial effects in the endothelium and in the cardiac tissue although the molecular mechanisms by which GLP-1 exerts these actions are still unknown. Recently, it has been demonstrated that SIRT1, a NAD’+ deacetylase protein, has a protective role on vascular damage in diabetes by reducing oxidative stress. In several cells and in animal models of diabetes SIRT1 gene expression is reduced. Therefore, SIRT1 may represent a new therapeutic target in the prevention of macrovascular complications of diabetes.
Aim: To investigate the effects of GLP-1 on SIRT1 gene expression in human umbelical vein endotelial cells (HUVEC) grown at normal and high glucose. Furthermore, we explored the molecular pathways by which GLP-1 may regulate SIRT1 gene expression.
Methods: HUVEC were cultured at 5.5 mM o 20 mM glucose in the presence/ absence of two GLP-1 peptides: GLP-1(7-37) and GLP-1(9-36)NH2. Gene expression of SIRT1 was assessed by RT-PCR real time. Akt, AMPK and ERK phosphorylation were measured by Western Blot.
Results: SIRT1 gene expression was significantly reduced in HUVEC grown at 20mM in comparison to cells grown at 5.5 mM of glucose. The treatment of cells with GLP-1(7-37) or with GLP-1(9-36)NH2 increased SIRT1 gene expression at 20mM glucose but not at 5.5 mM glucose. Furthermore, GLP-1(7-37) e GLP-1(9-36)NH2 enhanced two different intracellular pathways: GLP-1(7-37) stimulated Akt while GLP-1(9-36)NH2 activated AMPK.
Conclusions: SIRT1 is a new and promising therapeutic target for diabetes. The increase of SIRT1 expression by GLP-1 peptides opens new perspectives for the use of incretin therapy in the prevention of diabetic macrovascular complications. Furthermore, the evidence of different GLP-1-activated pathways allows us to hypothesize different mechanisms in the regulation of the expression of SIRT1Premesse: L'introduzione della terapia incretinica nella cura del diabete ha rivelato un potenziale ruolo protettivo di questi farmaci verso le comorlidità cardiovascolari. Il GLP-1 è dotato di effetti protettivi a livello endoteliale e cardiaco, ma i meccanismi molecolari attraverso i quali il GLP-1 esercita tali azioni sono solo in parte conosciuti. Recentemente, è stato dimostrato che SIRT1, una protein- deacetilasi NAD+dipendente, esercita un ruolo protettivo da danno vascolare nel diabete, attraverso la riduzione dello stress ossidativo cellulare. In diversi modelli cellulari e animali di diabete l'espressione genica di SIRT1 è ridotta. SIRT1, può dunque rappresentare un nuovo target terapeutico per la prevenzione delle complicanze macrovascolari nel diabete mellito.
Scopo: Valutare gli effetti di GLP-1 sull'espressione genica di SIRT1, in cellule endoteliali in condizioni di normoglicemia e di iperglicemia. Identificare, inoltre, le vie metaboliche attivate dal GLP-1, nella regolazione di SIRT1.
Metodi: Gli esperimenti sono stati eseguiti in vitro, in colture di cellule endoteliali (HUVEC). L'espressione genica di SIRT1 è stata misurata con RTPCR, in cellule HUVEC dopo trattamento con i peptidi di GLP-1, GLP-1(7-37) e GLP-1(9-36)NH2 in condizioni di normoglicemia (glucosio 5.5 mM) ed iperglicemia (glucosio 20mM). È stata successivamente valutata l'espressione proteica e l'attivazione delle vie Akt, AMPK ed ERK mediante western blot.
Risultati: L'espressione genica di SIRT1 è ridotta nelle cellule endoteliali in condizioni di iperglicemia. Entrambi i peptidi di GLP-1 sono in grado di normalizzare l'espressione genica di SIRT1 in condizioni di iperglicemia. In condizioni normoglicemiche non vi è alcun effetto di GLP-1 sull'espressione genica di SIRT1. Inoltre si è visto che i due peptidi stimolano due vie metaboliche differenti: il peptide GLP-1(7-37) attiva la via Akt, mentre il GLP-1(9-36)NH2 attiva la via AMPK.
Conclusioni: La normalizzazione dell'espressione genica di SIRT1 rappresenta un nuovo e promettente target terapeutico per il diabete mellito. La normalizzazione dell'espressione di SIRT1 da parte dei due peptidi GLP-1, apre nuove prospettive per l'impiego della terapia incretinica nella prevenzione delle complicanze macrovascolari nel diabete mellito. L'evidenza di due vie metaboliche differenti attivate dai due peptidi permette di ipotizzare dei meccanismi indipendenti da parte di GLP-1(7-37) e GLP-1(9-36)NH2 nella regolazione dell'espressione di SIRT1, aprendo la ricerca di nuovi bersagli molecolari per la terapia del diabete con GLP-
RGS2 expression and aldosterone: renin ratio modulate response to drug therapy in hypertensive patients
Full text linkObjective RGS2 (regulators of G-protein signalling) is a negative regulator of G(alpha q) protein signalling, which mediates the action of several vasoconstrictors. Low RGS2 expression increases G-protein-coupled signalling in hypertensive patients. The aim of the present study was to correlate RGS2 expression in peripheral blood mononuclear cells (PBMs) with response to antihypertensive therapy in never-treated patients with essential hypertension.
Methods and design RGS2 expression was measured by real-time quantitative RT-PCR in peripheral blood mononuclear cells (PBMs) from 102 essential hypertensives. The diagnosis of essential hypertension was based on all clinically required tests, including the captopril suppression test. Antihypertensive treatment was given in accordance to international guidelines. End-point of the study was systolic blood pressure (BP) less than 140mmHg and diastolic BP less than 90mmHg with three or less different antihypertensive agents, which identified responders to treatment. Resistant hypertension was defined as the failure to control systolic and/or diastolic BP despite at least three different classes of antihypertensive agents, including a diuretic.
Results During follow-up, 85 (83%) patients reached the end point (responders). Resistant hypertensives (n=17, 17%) were older, had higher baseline BP, plasma aldosterone and aldosterone : renin ratio (ARR) and lower plasma renin activity than patients who reached the end point. RGS2 was negatively correlated to systolic BP at enrolment and significantly lower in PBMs from resistant hypertensives in comparison with patients that reached BP goal. According to logistic regression analysis, high RGS2 expression was predictor of reaching BP goal, whereas high ARR after captopril, age and systolic pressure at enrolment were predictor of resistant hypertension.
Conclusion RGS2 expression affects the response to antihypertensive treatment. Reduced RGS2 expression contributes to resistance to antihypertensive agents through poor negative feedback on the effects of aldosterone and of other vasoactive agents. J Hypertens 28: 1104-1108 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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