1,721,033 research outputs found
Endothelial dysfunction and inflammation in ischemic stroke pathogenesis
No full textStroke is a heterogeneous disease, and within the broad category of brain ischemia and its subtypes vary dramatically in its etiology. The endothelium can regulate the vascular homeostasis by modulating processes of vascular dilation and constric-tion by producing and secreting cytokines and chemical mediators, and inflammation represents one of the most important factors that contribute to alteration in vessel structure and function by dysregulation of this fine bal-ance. Endothelial dysfunction means a basic determinant of the vascular damage, which can be identified in all different clinical subtypes of stroke, and, recently, it has been recognized as an interesting determinant of cerebrovas-cular risk. The entire spectrum of inflammatory processes is likely to act in concert, and cytokines are important mediators of stroke by inducing immunological/inflammatory reactions, which contribute to brain infarct progression as well as to the disease severity and outcome. Results from recent studies and ongoing and future researches will allow characterizing these complex mechanisms better and finally leading to innovative therapeutic strategies that may change the natural history of this severe and disabling disease significantly
Biomarkers in anderson–fabry disease
Get PDFFabry disease is a rare lysosomal storage disorder caused by a deficiency of α-galactosidase A, resulting in multisystemic involvement. Lyso-Gb3 (globotriaosylsphingosine), the deacylated form of Gb3, is currently measured in plasma as a biomarker of classic Fabry disease. Intensive research of biomarkers has been conducted over the years, in order to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. An interesting field of application of such biomarkers is the management of female heterozygotes who present difficulty in predictable clinical progression. This review aims to summarise the current evidence and knowledge about general and specific markers that are actually measured in subjects with confirmed or suspected Fabry disease; moreover, we report potential novel markers such as microRNAs. Recent proteomic or metabolomic studies are in progress bringing out plasma proteome profiles in Fabry patients: this assessment may be useful to characterize molecular pathology of the disease, to improve diagnostic process, and to monitor response to treatment. The management of Fabry disease may be improved by the identification of biomarkers that reflect clinical course, severity, and the progression of the disease
Lipoproteins in atherosclerosis process
No full textBackground: Dyslipidaemias is a recognized risk factor for atherosclerosis, however, new evidence brought to light by trials investigating therapies to enhance HDL-cholesterol have suggested an increased atherosclerotic risk when HDL-C is high. Results: Several studies highlight the central role in atherosclerotic disease of dysfunctional lipoproteins; oxidised LDL-cholesterol is an important feature, according to “oxidation hy-pothesis”, of atherosclerotic lesion, however, there is today a growing interest for dysfunctional HDL-cholesterol. The target of our paper is to review the functions of modified and dysfunctional lipoproteins in atherogenesis. Conclusion: Taking into account the central role recognized to dysfunctional lipoproteins, measurements of functional features of lipoproteins, instead of conventional routine serum evaluation of lipoproteins, could offer a valid contribution in experimental studies as in clinical practice to stratify atherosclerotic risk
Treatment of Anderson-Fabry disease
No full textFabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, predominantly globotriaosylsphingosine (Gb3) in lysosomes, as well as other cellular compartments of several tissues, causing multi-organ manifestations (acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement). Pathogenic mutations lead to a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). In the presence of high clinical suspicion, a careful physical examination and specific laboratory tests are required. Finally, the diagnosis of Fabry’s disease is confirmed by the demonstration of the absence of or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females. Measurement of the biomarkers Gb3 and Lyso Gb3 in biological specimens may facilitate diagnosis. The current treatment of Anderson-Fabry disease is represented by enzyme replacement therapy (ERT) and oral pharmacological chaperone. Future treatments are based on new strategic approaches such as stem cell-based therapy, pharmacological approaches chaperones, mRNA therapy, and viral gene therapy. This review outlines the current therapeutic approaches and emerging treatment strategies for Anderson-Fabry disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction: Regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications
Get PDFIschemic stroke occurs under a variety of clinical conditions and has different pathogeneses, resulting in necrosis of brain parenchyma. Stroke pathogenesis is characterized by neuroinflammation and endothelial dysfunction. Some of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells (microglia, astrocytes and endothelial cells), inflammatory cytokines, and translocation of intercellular nuclear factors. Inflammation in stroke includes all the processes mentioned above, and it consists of either protective or detrimental effects concerning the 'polarization' of these processes. This polarization comes out from the interaction of all the molecular pathways that regulate genome expression: the epigenetic factors. In recent years, new regulation mechanisms have been cleared, and these include non-coding RNAs, adenosine receptors, and the activity of mesenchymal stem/stromal cells and microglia. We reviewed how long non-coding RNA and microRNA have emerged as an essential mediator of some neurological diseases. We also clarified that their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke. To date, we do not have adequate tools to control pathophysiological processes associated with stroke. Our goal is to review the role of non-coding RNAs and innate immune cells (such as microglia and mesenchymal stem/stromal cells) and the possible therapeutic effects of their modulation in patients with acute ischemic stroke. A better understanding of the mechanisms that influence the 'polarization' of the inflammatory response after the acute event seems to be the way to change the natural history of the disease
Endothelial function and pathogenesis of endothelial dysfunction
No full textBackground: The crucial role of endothelium is due to the ability of endothelial cells to receive and concurrently respond to humoral and hemodynamic stimuli. The mechanisms that mediate these reactions are: the production of endothelium-derived factors and metabolizing enzymes; the expression of binding proteins and adhesive molecules; and the consequential shape changes. In fact, a wide range of anti-atherosclerotic action substances is produced by the endothelial cells with the objective of maintaining the balance between vasoconstriction and vasodilation, and inhibit or stimulate the proliferation and migration of smooth muscle cells, thrombogenesis and fibrinolysis. Smoke, age, hypercholesterolemia, hypertension, hyperglycemia, and a family history of atherosclerotic disease may induce functional and structural changes in the endothelium that imply the progressive loss of its protective role and the development of a proatherosclerotic state called endothelial dysfunction. Methods: The evaluation of the function of endothelial cells is based on the measurement of endothelial cell response to the stimulation by vasoactive substances. The endothelial response can be assessed in the coronary arteries and peripheral circulations. On our opinion, among the techniques, the most advantageous, reproducible, minimally invasive and statistically valid, as shown in many trials, is the Endo-PAT. This technique assesses endothelial function on peripheral arteries evaluating, at the level of the distal phalanx of the index finger, the vascular response to a period of ischemia in the arm induced through occlusion of the brachial artery (for five minutes) and subsequent restoration of blood flow. An additional method that is used to evaluate the state of wellness of large arteries is arterial stiffness. Arterial stiffness can be described as a reduced capability of a vessel to dilate or contract in response to pressure changes; it is defined using two parameters: compliance and distensibility. Result and Conclusion: The present review intends to clarify the mechanisms behind the development of endothelial dysfunction, and aims to show how widely proven is the correlation between endothelial dysfunction (assessed both by Endo-PAT and sphigmoCOR) and cardiovascular diseases, such as atherosclerosis, hypertension, diabetes mellitus, stroke, coronary artery disease and heart failure. Moreover, the assessment of endothelial dysfunction may represent an integral adjuvant test to identify the predisposed patients at risk for future cardiovascular accidents, as we suggest
Variations on the Author
Get PDF“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
Get PDFWe 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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