1,720,993 research outputs found

    Cisplatin ototoxicity and role of antioxidant on its prevention

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    Objective: Highlight the novelties of cisplatin ototoxicity and its prevention, focussing on the role of oxidative stress. Methods: We screened various electronic databases and selected the reports concerning clinical data and animal and in vitro models investigations related to cisplatin-induced ototoxicity and or its prevention by antioxidants. Results: Clinical evidence showed that great advances have been made in the chemotherapy outcomes; nevertheless, the ototoxicity, mainly in paediatric patients, is a crucial issue that must be solved. In vitro and in vivo models were pivotal to deeply describe the toxic effect of the cisplatin and which are the mechanisms of action. These knowledges will help the researcher to improve the chemotherapy protocols in order to avoid the adverse effects without compromise the antitumoral action. Conclusion: Antioxidants seem to be the most promising drugs among the large number of substances tested against cisplatin ototoxicity, however, the inflammatory pathway must be taken into consideration

    Acquired sensorineural hearing loss in children: current research and therapeutic perspectives. Sordità infantile acquisita: stato dell’arte della ricerca e prospettive terapeutiche

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    La conoscenza dei meccanismi fisiopatologici delle condizioni responsabili dell’ipoacusia acquisita nei bambini, tra cui le infezioni virali e batteriche, l’esposizione al rumore, l’ototossicità da chemioterapici ed antibiotici aminoglicosidici, è in costante aumento e sta portando ad un progressivo cambiamento della gestione diagnostica e clinica del bambino ipoacusico. Le infezioni virali rappresentano la causa più frequente di sordità infantile acquisita, seguita dalla tossicità di antibiotici e chemioterapici; mentre l’esposizione al rumore, soprattutto negli adolescenti, rappresenta un fattore emergente. Le terapie farmacologiche protettive attualmente in uso includono steroidi, antiossidanti, antivirali; l’efficacia degli antiossidanti è ancora in fase di conferma clinica anche se vi sono significative evidenze sperimentali, mentre i farmaci steroidei ed antivirali sono certamente validi seppur la loro tossicità sistemica rappresenti ancora un problema non chiarito per i quali la somministrazione locale potrebbe rappresentare una possibile evoluzione. Le prospettive di ricerca future includono l’uso di nanoparticelle per veicolare molecole direttamente nel sito di danno; inoltre, la terapia genica con l’inserimento di materiale genetico all’interno delle cellule per la cura di condizioni da alterazione del patrimonio genetico con la produzione di proteine normali, potrebbe svolgere un ruolo rilevante nella cura e soprattutto nella prevenzione delle sordità acquisite; infine, la terapia rigenerativa e l’impianto delle cellule staminali, nonostante il loro ruolo nell’orecchio interno sia ancora dibattuto, per le notevole limitazioni del loro impiego, potrebbe trovare un ruolo nei processi riparativi più che nella differenziazione in cellule sensorialiThe knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic. Pharmacological approaches are still challenging to develop a truly effective cochlear protection; however, the use of steroids, antioxidants, antiviral drugs and other small molecules is encouraging for clinical practice. Most of evidence on the effectiveness of antioxidants is still limited to experimental models, while the use of corticosteroids and antiviral drugs has a wide correspondence in literature but with controversial safety. Future therapeutic perspectives include innovative strategies to transport drugs into the cochlea, such as molecules incorporated in nanoparticles that can be delivered to a specific target. Innovative approaches also include the gene therapy designed to compensate for abnormal genes or to make proteins by introducing genetic material into cells; finally, regenerative medicine (including stem cell approaches) may play a central role in the upcoming years in hearing preservation and restoration even if its role in the inner ear is still debate

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Pioglitazone represents an effective therapeutic target in preventing oxidative/inflammatory cochlear damage induced by noise exposure.

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    Recent progress in hearing loss research has provided strong evidence for the imbalance of cellular redox status and inflammation as common predominant mechanisms of damage affecting the organ of Corti including noise induced hearing loss. The discovery of a protective molecule acting on both mechanisms is challenging. The thiazolidinediones, a class of antidiabetic drugs including pioglitazone and rosiglitazone, have demonstrated diverse pleiotrophic effects in many tissues where they exhibit anti-inflammatory, anti-proliferative, tissue protective effects and regulators of redox balance acting as agonist of peroxisome proliferator-activated receptors (PPARs). They are members of the family of ligand regulated nuclear hormone receptors that are also expressed in several cochlear cell types, including the outer hair cells. In this study, we investigated the protective capacity of pioglitazone in a model of noise-induced hearing loss in Wistar rats and the molecular mechanisms underlying this protective effects. Specifically, we employed a formulation of pioglitazone in a biocompatible thermogel providing rapid, uniform and sustained inner ear drug delivery via transtympanic injection. Following noise exposure (120 dB, 10 kHz, 1 h), different time schedules of treatment were employed: we explored the efficacy of pioglitazone given immediately (1 h) or at delayed time points (24 and 48 h) after noise exposure and the time course and extent of hearing recovery were assessed. We found that pioglitazone was able to protect auditory function at the mid-high frequencies and to limit cell death in the cochlear basal/middle turn, damaged by noise exposure. Immunofluorescence and western blot analysis provided evidence that pioglitazone mediates both anti-inflammatory and anti-oxidant effects by decreasing NF-κB and IL-1β expression in the cochlea and opposing the oxidative damage induced by noise insult. These results suggest that intratympanic pioglitazone can be considered a valid therapeutic strategy for attenuating noise-induced hearing loss and cochlear damage, reducing inflammatory signaling and restoring cochlear redox balance. Copyright © 2018 Paciello, Fetoni, Rolesi, Wright, Grassi, Troiani and Paludetti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

    Antioxidant protection against acoustic trauma by coadministration of idebenone and vitamin E

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    Idebenone, a synthetic analogue of coenzyme Q, attenuates noise-induced hearing loss by virtue of its antioxidant properties. This study involves a guinea pig model of acoustic trauma where the effectiveness of idebenone is analyzed in comparison with Vitamin E (α-tocopherol) that exhibits a potent antioxidant activity in the inner ear. Idebenone and vitamin E were injected intraperitoneally 1 h before noise exposure and once daily for three days; functional and morphological studies were then carried out, respectively, by auditory brainstem responses evaluation, scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay identification of missing and apoptotic cells was also performed. The results showed that the protective effects of idebenone and vitamin E were not additive implying that the two antioxidants may share competitive mechanisms. © 2008 Lippincott Williams & Wilkins, Inc

    Variations on the Author

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    “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

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    We 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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