1,721,119 research outputs found
Ruolo della fosfolipasi A2 secretoria e della fosfolipasi associata alle lipoproteine nel rischio cardiovascolare
No full textPhospholipase A2(PLA2) are enzymes that hydrolyze the ester bond of glycerophospholipids releasing free fatty acids and lysophospholipids, including the arachidonic acid, the precursor of the eicosanoids and the inflammatory cascades. PLA2are present in the atherosclerotic plaques and their direct involvement in the proatherogenic inflammatory response is well documented. Epidemiological and genetic studies have demonstrated the correlation of the PLA2 mass and enzymatic activity with the incidence of cardiovascular diseases. The potential pro-atherogenic role of PLA2led to the development of two small molecules, varespladib, a reversible sPLA2 inhibitor, and darapladib, a selective Lp-PLA2inhibitor. Both molecules have demonstrated antiatherosclerotic properties in animal models, and positive effects on atherosclerotic plaque composition evaluated in phase 2 clinical trials. On these grounds, the results of three phase 3 studies have recently been published: the VISTA-16 study with varespladib in patients with acute coronary syndrome, and the STABILITY and SOLID-TIMI 52 studies with darapladib in patients with stable coronary heart disease and acute coronary syndrome, respectively. Unexpectedly, both studies did not demonstrate an additional protective action of PLA2inhibitors over the standard of care treatment with statins, antiplatelet drugs, and coronary revascularization.In the present article, the enzymatic properties and the involvement of sPLA2 and Lp-PLA2in atherogenesis are reviewed, with a focus on the results of experimental studies and clinical studies with both varespladib and darapladib inhibitors
Clinical evidence of statin therapy in non-dyslipidemic disorders
No full textThe clinical benefits of statins are strongly related to their low density lipoprotein cholesterol (LDL-C) lowering properties. However, considering that the pharmacological target of statins, the 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase, is one of the upstream enzyme of the mevalonate pathway, its inhibition may determine a substantial impoverishment of additional lipid moieties required for a proper cellular function. From this hypothesis, several experimental and clinical evidences have been reported indicating additional effects of statins beyond the LDL-C lowering, in particular anti-inflammatory and immunomodulatory effects. Thus statin therapy, indicated for hyperlipidemic patients for primary and secondary prevention of coronary heart disease (CHD) has begun to be considered effective in other diseases not necessarily linked to altered lipid profile. In the present review we summarized the current clinical evidence of the efficacy and safety profile of statins in a variety of diseases, such as rheumatoid arthritis, venous thromboembolism, liver diseases, polycystic ovary syndrome, and age-related macular degeneration. As discussed in the review, pending large, well designed, randomized trials, it is reasonable to conclude that there is no definitive evidence for the use of statins in the aforementioned diseases
Edoxaban and the Issue of Drug-Drug Interactions: From Pharmacology to Clinical Practice
No full textEdoxaban, a direct factor Xa inhibitor, is the latest of the non-vitamin K antagonist oral anticoagulants (NOACs). Despite being marketed later than other NOACs, its use is now spreading in current clinical practice, being indicated for both thromboprophylaxis in patients with non-valvular atrial fibrillation (NVAF) and for the treatment and prevention of venous thromboembolism (VTE). In patients with multiple conditions, the contemporary administration of several drugs can cause relevant drug-drug interactions (DDIs), which can affect drugs' pharmacokinetics and pharmacodynamics. Usually, all the NOACs are considered to have significantly fewer DDIs than vitamin K antagonists; notwithstanding, this is actually not true, all of them are affected by DDIs with drugs that can influence the activity (induction or inhibition) of P-glycoprotein (P-gp) and cytochrome P450 3A4, both responsible for the disposition and metabolism of NOACs to a different extent. In this review/expert opinion, we focused on an extensive report of edoxaban DDIs. All the relevant drugs categories have been examined to report on significant DDIs, discussing the impact on edoxaban pharmacokinetics and pharmacodynamics, and the evidence for dose adjustment. Our analysis found that, despite a restrained number of interactions, some strong inhibitors/inducers of P-gp and drug-metabolising enzymes can affect edoxaban concentration, just as it happens with other NOACs, implying the need for a dose adjustment. However, our analysis of edoxaban DDIs suggests that given the small propensity for interactions of this agent, its use represents an acceptable clinical decision. Still, DDIs can be significant in certain clinical situations and a careful evaluation is always needed when prescribing NOACs
PCSK9 sustains SMC synthetic phenotype, proliferation and migration capacity in response to PDGF: possible role on neointimal formation after perivascular carotid collar placement in mice
No full textClinical Pharmacology of Statins: an Update
Full text linkStatins represent the cornerstone for the treatment of hypercholesterolemia, although muscle-related side effects and dysregulation of glucose metabolism have strongly limited their adherence and compliance especially in primary prevention therapy. The purpose of the present review is to provide the most recent evidence of the efficacy and safety of statins in monotherapy or combination with new lipid-lowering drugs
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
Drug-Drug Interactions of FXI Inhibitors: Clinical Relevance
Full text link: Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug-drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa
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
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