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    Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers J. Controlled Rel.

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    The aim of this work was the evaluation of various ethosomal suspensions made up of water, phospholipids and ethanol at various concentrations for their potential application in dermal administration of ammonium glycyrrhizinate, a useful drug for the treatment of various inflammatory-based skin diseases. Physicochemical characterization of ethosomes was carried out by photon correlation spectroscopy and freeze fracture electron microscopy. The percutaneous permeation of ammonium glycyrrhizinate/ethosomes was evaluated in vitro through human stratum corneum and epidermis membranes by using Franz’s cells and compared with the permeation profiles of drug solutions either in water or in a water–ethanol mixture. Reflectance spectrophotometry was used as a non-invasive technique to evaluate the carrier toxicity, the drug permeation and the anti-inflammatory activity of ammonium glycyrrhizinate in a model of skin erythema in vivo on human volunteers. Ethosomal suspensions had mean sizes ranging from 350 nm to 100 nm as a function of ethanol and lecithin quantities, i.e., high amounts of ethanol and a low lecithin concentration provided ethosome suspensions with a mean size of ~100 nm and a narrow size distribution. In vitro and in vivo experiments were carried out by using an ethosome formulation made up of ethanol 45% (v/v) and lecithin 2% (w/v). The ethosome suspension showed a very good skin tolerability in human volunteers, also when applied for a long period (48 h). Ethosomes elicited an increase of the in vitro percutaneous permeation of both methylnicotinate and ammonium glycyrrhizinate. Ethosomes were able to significantly enhance the anti-inflammatory activity of ammonium glycyrrhizinate compared to the ethanolic or aqueous solutions of this drug. Somein vivo experiments also showed the ability of ethosome to ensure a skin accumulation and a sustained release of the ammonium glycyrrhizinate. D 2005 Elsevier B.V. All rights reserved. Keywords: Ethosomes; In vitro percutaneous permeation; Methyl nicotinate; Ammonium glycyrrhizinate; In vivo evaluatio

    Incidenza della mutazione rs12979860 del gene di IL28 in un gruppo di soggetti HCV positivi dell’U.O.C. di Malattie infettive del P.O. Civico di Palermo

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    L'infezione cronica da HCV colpisce 170 milioni di persone in tutto il mondo;su 100 persone infettate dal virus HCV il 15% non sviluppa alcuna patologia cronica ed elimina il virus, il restante 85% sviluppa forme croniche della malattia con evoluzione in cirrosi epatica e in carcinoma epato-cellulare.Il trattamento dell'epatite C cronica, che offre i maggiori vantaggi, è rappresentato da un ciclo di 24-48 settimane di PEG-Interferone-alfa-2a e Ribavirina. Il suo esito è influenzato da una serie di fattori tra cui il genotipo virale ed alcuni polimorfismi genetici dell’ospite I pazienti infetti da HCV di genotipo 2 o 3 hanno probabilità 2-3 volte maggiore di rispondere alla terapia rispetto a coloro che sono infettati dal genotipo 1.Nell’ospite le variazioni geniche dell' IL28 sono associate alla risposta virale al trattamento dell’HCV con PEG-Interferone-alfa-2a e Ribavirina. La presenza del polimorfismo SNP “rs 12979860” determina una sostituzione C/T nella sequenza del promotore a monte del gene umano che codifica per la citochina “IL28” localizzato sul cromosoma 19 la cui espressione è indotta ed attivata dalle infezioni virali. Il polimorfismo IL28 B non solo influenza direttamente la risposta del paziente al trattamento ma ne determina il dosaggio terapeutico in funzione del genotipo stesso. E' stato dimostrato come infatti vi siano genotipi favorevoli al trattamento (C-C) e genotipi meno favorevoli (C-T e T-T). Nel nostro studio abbiamo valutato l’espressione delle mutazioni su un gruppo di 40 pazienti afferenti all’U.O.C. di Malattie infettive del P.O. Civico , affetti da infezione da HCV e candidati a terapia con IFN e RBV .La ricerca è stata effettuata con tecnica in real-time ed ha fornito i seguenti risultati : 12 pazienti postivi (30% ) per genotipo CC suscettibili a terapia e 28 (70%) con genotipo meno favorevole ( CT o TT ) per i quali si dovrà valutare il potenziale impiego dei farmaci antivirali emergenti

    Chelation treatment in sickle-cell-anaemia: much ado about nothing?

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    Blood transfusions may prevent and treat serious complications related to sickle-cell disease (SCD) when performed according to specific guidelines. However, blood transfusion requirements in SCD inevitably lead to increased body iron burden. An adequate chelation treatment may prevent complications and reduce morbidity and mortality. This review evaluates the effectiveness, safety and costs of chelation treatment. The included trials were examined according to the recommendations of the American College of Cardiology (ACC) and the American Heart Association (AHA). Overall, 14 trials and a total of 502 patients with SCD were included in this review. Deferoxamine alone (s.c. or i.v.), deferiprone alone or versus deferoxamine, deferasirox versus deferoxamine and combined treatment with deferoxamine plus deferiprone were included and evaluated in the analysis. Only two randomized clinical trials have been reported. The results of this analysis suggest that use of chelation treatment in SCD to date has been based on little efficacy and safety evidence, although it is widely recommended and practised. The cost/benefit ratio has not been fully explored. Further research with larger randomized clinical trials needs to be performed

    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

    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

    FORMULATIONS OF RETINYL PALMITATE INCLUDED IN SOLID LIPID NANOPARTICLES: CHARACTERIZATION AND INFLUENCE ON LIGHT-INDUCED VITAMIN DEGRADATION

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    The therapeutic use of retinoids is still limited because of adverse effects and their chemical instability due to moisture, oxygen, acids, metals and light exposure. The purpose of this research was to investigate particulate carrier systems such as solid lipid nanoparticles (SLNs) for formulation of vitamin A palmitate. SLN (Precirol ATO 5, Pluronic F68, sodium cholate) were obtained using the hot homogenization technique and sonication, and were characterized using freeze fracture microscopy, dynamic light scattering, for size and zeta potential measurements and DSC. SLN formulation was optimized by modifying surfactant mixture composition to obtain better SLN physical stability and better vitamin entrapment efficiency. Preferential vitamin disposition on particle surface was evaluated by DSC analyses and release studies. RetP stability studies were carried out using normal phase HPLC on samples exposed continuously, in a darkened room, to the light of a filament lamp (400 lux) and the influence of the inclusion in solid lipid nanoparticles on retinyl palmitate (RetP) light-induced degradation was evaluated in the presence and absence of conservative agent (BHA, 3-tert-butyl-4-idroxi-anisole). The Precirol ATO 5 SLN formulation of RetP offers high entrapment efficiency but does not offer the possibility of preventing photo-degradation of RetP. In the nanoparticulate structures analyzed, RetP is preferentially distributed to the surface of the particles and partially exposed to external aqueous phase, thus no protection from RetP degradation can be evidenced in comparison to reference RetP solution (THF:water 9:1 v:v

    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

    LA FARMACOGENOMICA NELLA VALUTAZIONE DEL RISCHIO DA CHEMIOTERAPIA: POLIMORFISMI GENICI E 5-FLUOROURACILE NEL TRATTAMENTO DEL CARCINOMA DEL COLON-RETTO

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    Introduzione: Il 5-fluorouracile (5-FU) ed il suo profarmaco capecitabina, attivo per via orale, è usato nel trattamento di numerosi tumori solidi, tra cui carcinomi mammari, colo-rettali e della regione testa-collo. Nonostante la sua efficacia, a suo carico sono stati associati fenomeni di grave tossicità correlati all’enzima diidropirimidina deidrogenasi (DPD), responsabile del suo metabolismo,la cui carenza determina un profondo ritardo nell’eliminazione dell’agente chemioterapico.Pertanto la presenza di polimorfismi nella regione codificante del gene DPYD può determinare lo sviluppo di gravi tossicità di III-IV grado, come: nausea, vomito, diarrea, stomatiti, leucopenia, neutropenia, piastrinopenia, anemia e sindrome mano-piede

    Dispelling the Myths Behind First-author Citation Counts

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    We 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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