1,720,980 research outputs found
Non Alcoholic Fatty Liver Disease: non invasive markers of severity and new experimental treatments
Full text linkNon Alcoholic Fatty Liver Disease (NAFLD) is a worldwide increasing disease but still many questions about its evolution, the need of a screening and the availability of effective specific treatments are open.
Aims of this PhD project were:
1) the evaluation of NAFLD natural history in a subgroup of NAFLD affected diabetic patients enrolled during the daily clinical activity of a splenohepatology ecoDoppler laboratory in order to identify, if present, predictive factors of “evolutive NAFLD”;
2) the experimental evaluation, in High Fat Diet (HFD) fed rats, of the potential therapeutic effect of 3 molecules
targeting respectively:
a) lipid metabolism (Apolipoprotein A analogue compound -L4F),
b) insulin sensitivity (peroxisome proliferator activated receptor delta agonist –PPARd agonist)
c) endothelial function (EET Analog).
We developed two studies: a clinical observational study and an experimental study.
Clinical study:
100 patients with type 2 diabetes were evaluated as far as steatosis is concerned. Among them, 80 had sonographic signs of steatosis. There was no difference in the prevalence between male and female patients. 21 type 2 diabetic patients with liver steatosis were reevaluated after 6 years without any specific treatment. Liver steatosis increases only in less than 1/3 of non-obese diabetic patients and demonstrates that in the majority of them sonographic degree of steatosis improves or recovers concurrently with biohumoral parameters. The presence of increased levels of serum AST and ferritin and lower pulsatility index of haepatic artery seems to be correlated to a worse prognosis and may be used to identify those patients who deserve a higher surveillance.
Experimental study:
30 male Wistar rats (4-5 weeks old, 150 grams body weight) were purchased from Charles River Laboratories. 24 rats have been fed with HFD for 8 weeks. After 8 weeks of diet animals have been divided in 4 groups: 7 untreated (HFD); 7 treated with L4F (L4F), 7 treated with PPARd agonist (PPARd) and 3 treated with EET Analog (EET). Treatments lasted 6 weeks. We demonstrate that HFD induced NAFLD reproduces splanchnic haemodynamic alteration of liver steatosis in humans and shows an activation of innate immune system also at early degree of steatosis without hepatic inflammation and fibrosis. The activation of innate immune system can be evaluated by the analysis of lipopolysaccharide (LPS) stimulated/unstimulated CC motif chemockine ligand 2 (CCL2) production in cultured peripheral blood mononuclear cells (PBMCs).
PPARd agonist and L4F improved HFD induced liver steatosis and reduced CCL2 production in PBMCs but preserved the ability of PBMCs to react to LPS stimulation EETA administration didn’t improved liver steatosis and further decreased portal vein velocity and reduced the ability of PBMCs to react to LPS stimulation
EETs and HO-1 cross-talk
No full textEpoxygenase-dependent metabolites of arachidonc acid, EETs and the heme-oxygenase (HO)-1/carbon monoxide/bilverdin system share similarities in their activity and mediators. They control endothelial function, dilating small arterial vessels, decrease blood pressure, protect the heart from ischemic and hypertensive cardiopathy, control renal circulation and function, promote angiogenesis and organ regeneration, oppose oxidative stress and inflammation, improve diabetes and obesity, have protective effects on the liver, and participate in portal hypertension. Furthermore, EETs induce HO-1, and inhibition of HO-1 abolishes most of the effects of EETs. Thus, a close interaction between the two systems exists, and is relevant in view of their therapeutic potential
EETs and HO-1 cross-talk
No full textEpoxygenase-dependent metabolites of arachidonc acid, EETs and the heme-oxygenase (HO)-1/carbon monoxide/bilverdin system share similarities in their activity and mediators. They control endothelial function, dilating small arterial vessels, decrease blood pressure, protect the heart from ischemic and hypertensive cardiopathy, control renal circulation and function, promote angiogenesis and organ regeneration, oppose oxidative stress and inflammation, improve diabetes and obesity, have protective effects on the liver, and participate in portal hypertension. Furthermore, EETs induce HO-1, and inhibition of HO-1 abolishes most of the effects of EETs. Thus, a close interaction between the two systems exists, and is relevant in view of their therapeutic potential
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
Arachidonic acid metabolites and endothelial dysfunction of portal hypertension
No full textIncreased resistance to portal flow and increased portal inflow due to mesenteric
vasodilatation represent the main factors causing portal hypertension in
cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the
synthesis, release, and effect of endothelial mediators of vascular tone,
inflammation, thrombosis, and angiogenesis, plays a major role in the increase of
resistance in portal circulation, in the decrease in the mesenteric one, in the
development of collateral circulation. Reduced response to vasodilators in liver
sinusoids and increased response in the mesenteric arterioles, and, viceversa,
increased response to vasoconstrictors in the portal-sinusoidal circulation and
decreased response in the mesenteric arterioles are also relevant to the
pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through
the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450
monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal
hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial
cells (LSECs) via increased COX-1 activity/expression, increased leukotriens,
increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial
circulation, but vasoconstrictors of the portal-sinusoidal circulation),
represent a major component in the increased portal resistance, in the decreased
portal response to vasodilators and in the hyper-response to vasoconstrictors.
Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased
EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived
hyperpolarizing factor system) play a major role in mesenteric vasodilatation,
hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs,
mediators of liver regeneration after hepatectomy and of angiogenesis, may play a
role in the development of regenerative nodules and collateral circulation,
through stimulation of vascular endothelial growth factor (VEGF) inside the liver
and in the portal circulation. Pharmacological manipulation of AA metabolites may
be beneficial for cirrhotic portal hypertension
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
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