1,721,051 research outputs found
New Pyrolle and Pyrazole based compounds active as anti-inflammatory and antimalarial drugs
Full text linkThis thesis addresses the urgent requirement for novel anti-inflammatory drugs and antimalarial interventions:
The beneficial effects of carbon monoxide (CO) gained much interest in research and offer new potential treatments of vascular- and inflammatory-related diseases. However, the medical application of this gas has been hampered by the complexity of the administration route. This problem has been overcome with the discovery of CO-releasing molecules (CORMs), which are an effective tool to deliver CO safely and precisely to the target locations. Particularly, metal-based CORMs are emerging for their striking anti- inflammatory properties that are amplified by the transition metal and are being progressively improved in view of novel future applications.
We developed novel dual-active metal-based CORMs with the potential to be used as therapeutic agents in tendon-derived diseases. Specifically, we designed and synthesized dicobalt(0)hexacarbonyl (DCH)-CORMs containing structural fragments of COX-2 selective inhibitors and tested them for the CO release kinetic (myoglobin release assay) and anti- inflammatory/cytoprotective effects on hydrogen peroxide-stimulated human primary- derived tenocytes by taking in account the PGE2 secretion as a readout.
Malaria drug research and development efforts have recently resurged in the last decade following deceleration rate of mortality and malaria cases in endemic regions. Inefficiency of malaria interventions are largely driven by the spreading resistance of the Plasmodium falciparum parasite to the current drug regimens and from the malaria vector – mosquito Anopheles – to insecticides. In response to the new eradication agenda, the development of drugs that act by breaking the malaria transmission cycle (transmission-blocking drugs) has been recognized as an important and additional target for intervention. These drugs take advantage of the susceptibility of Plasmodium population bottlenecks before transmission (gametocytes) and in the mosquito vector (gametes, zygotes, ookinetes, oocysts,
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sporozoites). In this context, we sought to address the urgent requirement for novel antimalarial interventions by developing and aiding future discovery of transmission- blocking drugs.
We designed and synthesized analogues of the pyrazole MMV1580843, recently discovered in a high-throughput screening as a potent and selective gametocytocidal compound. SAR studies of these compounds hold promise for improved chemical modifications to progress to a hit-to-lead campaign. Particularly, we found that the pyrazole core allows a variety of substitutions that maintain potent activity towards late-stage gametocytes along with favorable physicochemical and safety profiles.
In parallel, from a phenotypic screening of compounds belonging to an in-house library, we discovered new pyrazole- and pyrrole-based compounds endowed with selective activity towards ring and trophozoite stages in the P. falciparum asexual cycle and potential activity against sporogonic stages in mosquitoes. The transmission-blocking potential was assessed by performing topical exposure assays on females Anopheles Gambiae mosquitoes of selected hits and found compound 19 and 12 to significantly decrease the parasite development in the mosquito midgut
Immunosuppressive therapy in inflammatory cardiomyopathy
No full textThe role of immunosuppressive treatment in inflammatory cardiomyopathy is still controversial. Nevertheless, it is recommended in patients with eosinophilic myocarditis, granulomatous myocarditis, giant-cell myocarditis and lymphocytic myocarditis associated with connective tissue diseases or with rejection of a transplanted heart. There is growing evidence that some patients with idiopathic active myocarditis and cardiac dysfunction may benefit from immunosuppression. In the present review we define, through analysis of recent reports and the results of our own studies, the biological markers of candidates for immunosuppression. (C) 2002 The European Society of Cardiology
The role of endomyocardial biopsy in the diagnosis of cardiomyopathies
No full textThough many publications in the field of myocarditis and cardiomyopathies have renewed interest in the value of endomyocardial biopsy, its role in the work-up of patients with cardiomyopathies, idiopathic arrhythmias and even ischemic heart disease, is still debated. Since its introduction in 1963 the technique has been developed with current routine use of a biventricular and even atrial approach. At the same time immunohistochemistry and molecular biology studies have greatly enhanced the information obtainable from myocardial samples. The authors report their experience and briefly review the pertinent literature on the current use of endomyocardial biopsy in the diagnosis and treatment of dilated, hypertrophic and restrictive cardiomyopathy, of idiopathic arrhythmias and in ischemic heart disease
Idiopathic myocardial vasculitis presenting as restrictive cardiomyopathy
No full textA previously unreported case of small-vessel myocardial vasculitis presenting as restrictive cardiomyopathy and congestive heart failure is described. The hemodynamic study, showing severely increased and equalized diastolic pressures in atrial and ventricular chambers, and cardiac MRI, showing normal pericardium and ventricular endomyocardial biopsy, not including myocardial vascular component, were insufficient to make a diagnosis. This made a thoracotomy and surgical cardiac biopsy necessary. Steroids and cyclophosphamide, introduced after histologic evidence of necrotizing vasculitis, unassociated with a systemic disease, became available and improved the clinical profile and the diastolic dysfunction at two-dimensional echocardiographic Doppler analysis
Endomyocardial fibrosis mimicking a dilated cardiomyopathy in a child
No full text[No abstract available
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
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