1,720,956 research outputs found
Development of a new depigmenting cosmetic formulation
No full textSkin hyperpigmentation disorders, first melasma, remain a challenge in dermatology and cosmetics. To date no specific treatment has solved and reached adequate amelioration, in part because of the incomplete understanding of melasma pathogenesis and of the involved biological mechanisms. The complexity of skin melanogenesis derives from the multiple signalling pathways regulating the production of melanin in melanocytes and its transfer to keratinocytes as well as from the strict communication among skin and inflammatory cells by means of several paracrine factors produced in response to endogenous and exogenous stimuli, mainly UV radiation (UVR).
The main aim of this study was to generate an innovative cosmetic formulation for the topical treatment of melasma by combining molecules with different potential impact on skin melanogenesis. To this purpose, we selected α-arbutin and tranexamic acid (TXA), as active components of the new formulation. Arbutin is an “old” whitening agent, known for its ability to inhibit tyrosinase, the main enzyme involved in melanin biosynthesis. TXA is mainly known as an inhibitor of the plasminogen-plasmin system with potential anti-inflammatory activities and as a potent antifibrinolytic agent is commonly used in several surgical conditions. The interest in this molecule is based on its safe profile and the results of some previous papers showing the ability, mainly by oral assumption, in reducing skin pigmentation in melasma, although its cellular effects and mechanism of action are poorly known. The active principles were combined in a microemulsion, a delivery system known for its high skin penetration ability, compared with other cosmetic formulations. According to the current cosmetic regulation, the product has been analysed for its properties showing high physico-chemical and microbiological stability, absence of potential side effect and an optimal safety profile. Further, evaluation of the in vitro effects of TXA and α -arbutin effects was performed in in vitro experiments by using cell lines, representative of skin and inflammatory cells. Data obtained show that TXA has multiple biological functions that potentially may impact on in vivo melanogenesis. Notably, we have identified a melanocyte direct TXA inhibitory effect on melanin production in B16 cells, additive to that induced by α-arbutin, suggesting that the combination of the two molecules may induce better outcomes than each single compound used alone. Interestingly, for the first time in mouse macrophage cell line we have shown that TXA inhibited the LPS-induced release of proinflammatory molecules with promelanogenic activities, indicating interference among TXA and inflammatory events related to toll-like receptor (TLR) activation. As TLRs are involved in melanogenesis, as well as in other inflammatory skin diseases, we retain these data deserve further investigation.
Finally, we have conducted a pilot clinical trial in melasma-affected patients and evaluated the in vivo whitening effect of the new formulation. Dermatological evaluation of the MASI score, typically used for measurement of efficacy, has shown a 21% improvement, in line with published data obtained with other TXA treatments. Patient response has been confirmed by the recent VISIA® system, gaining information on the effect of the product for specific aspects of melasma affected skin.
Based on data collected in this study, the new whitening microemulsion can be considered already available for the following phases of the industrial development including manufacturing and placing on the market. We retain that the new generated product could represent an interesting novel therapeutic strategy for melasma treatment and potentially other skin diseases.I disordini di iperpigmentazione cutanea rappresentano una costante sfida in dermatologia e cosmetologia. La complessità del processo di melanogenesi nella pelle deriva dalle molteplici vie di segnalazione che regolano la produzione di melanina nei melanociti ed il suo trasporto nei cheratinociti, e da una complessa comunicazione tra i diversi tipi di cellule della pelle e cellule infiammatorie tramite fattori paracrini, prodotti in risposta a stimoli endogeni ed esogeni, in particolar modo le radiazioni UV (UVR).
L’obiettivo principale del presente studio è stato la realizzazione di una nuova formulazione cosmetica per il trattamento topico del melasma, attraverso la combinazione di molecole con un diverso potenziale impatto sulla melanogenesi. A tale scopo, abbiamo selezionato α-arbutina (α-Arb) e acido tranexamico (TXA) quali componenti attivi della nuova formulazione. α-Arb è un “vecchio” attivo schiarente, conosciuto per la sua capacità di inibire la tirosinasi, il principale enzima coinvolto nel processo di biosintesi di melanina. Il TXA è prevalentemente noto come inibitore del sistema plasminogeno-plasmina con potenziali attività antinfiammatorie e come potente agente antifibrinolitico è largamente usato in chirurgia. L’interesse per questa molecola è basato sul suo profilo tossicologico sicuro, ed i risultati di alcuni studi pregressi che hanno dimostrato la sua capacità, per lo più tramite assunzione orale, di ridurre la pigmentazione in soggetti affetti da melasma. Tuttavia, i suoi effetti a livello cellulare ed i meccanismi d’azione sono poco noti. I componenti attivi sono stati aggiunti in una microemulsione, un sistema di delivery conosciuto per la sua alta capacità di penetrazione. Il prodotto è stato analizzato per le sue caratteristiche, dimostrando un’alta stabilità chimico-fisica e microbiologica, l’assenza di potenziali effetti collaterali ed un ottimo profilo di sicurezza. Inoltre, sono stati condotti esperimenti in vitro valutando gli effetti di TXA e α-Arb attraverso l’utilizzo di linee cellulari, rappresentative dei tipi cellulari della pelle e di cellule infiammatorie. I dati ottenuti hanno dimostrato che il TXA ha molteplici funzionalità biologiche con potenziale impatto sul processo di melanogenesi in vivo. In particolare, abbiamo identificato un effetto inibitorio diretto nelle cellule B16 di melanoma, sulla produzione di melanina da parte di TXA, con azione sinergica all’inibizione indotta da α-Arb. Questo risultato suggerisce che la combinazione delle due molecole possa indurre effetti migliori rispetto ai singoli componenti usati separatamente. Per la prima volta è stato osservato che il TXA può inibire la produzione di molecole infiammatorie, con attività promelanogeniche, suggerendo una possibile interazione tra il TXA ed i processi infiammatori associati all’attivazione dei toll-like receptors (TLRs).
Infine, è stato condotto uno studio clinico pilota in pazienti affetti da melasma ed è stato valutato l’effetto schiarente della nuova formulazione in vivo. La valutazione dermatologica è stata effettuata tramite il parametro MASI, tipicamente usato per la misurazione dell’efficacia, che ha dimostrato un miglioramento significativo del 21%, in linea con alcuni studi pregressi. La risposta dei pazienti è stata inoltre confermata tramite il sistema innovativo VISIA®, che ha prodotto informazioni per specifici aspetti della pelle affetta da melasma.
Basandoci sui dati ottenuti in questo studio, la microemulsione realizzata può essere considerata attualmente disponibile per le prossime fasi dello sviluppo industriale, che comprendono la produzione e il posizionamento sul mercato. Si ritiene che il nuovo prodotto possa rappresentare una nuova ed interessante strategia terapeutica per il trattamento del melasma e potenzialmente per altre patologie dermatologiche
Bis(dimethylsulfoxide)carbonateplatinum(II), a new synthon for a low-impact, versatile synthetic route to anticancer Pt carboxylates
No full textThe work describes a new low-impact synthetic route to Pt(ii)-carboxylate complexes, a class of compounds provided with established anticancer activity. The process is based on the ligand substitution on [PtCO3(Me2SO-S)2] (1), a new synthon that can be easily prepared in water with high yield, is stable as a solid, and is reactive in solution where all its ligands can be easily replaced. It reacts with acidic O-donors releasing CO2 as the only side-product, whose development also supplies a driving force toward the products. The substitution of carbonate led to new Pt-DMSO carboxylate complexes 2-4, while the total substitution of the ligands of complex 1 gave new Pt-phosphino carboxylates 5-9 in high yields. The X-ray crystal structures of complexes [Pt(d(-)-quinate-O,O′)(Me2SO-S)2] (3), [Pt(salicylate)(Me2SO-S)2] (4) and [Pt(salicylate)(PPh3)2] (6) were determined. The tests of the antiproliferative activity of complexes 1-9 on two human tumoral cell lines, A2780 (cisplatin-sensitive) and SKOV-3 (cisplatin-resistant), showed that the PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) complexes 7-9 were the most active on both cell lines
Synthesis and characterization of Pt complexes containing dichloroacetate (DCA), designed for dual anticancer action
No full textA group of new Pt(II) complexes with dichloroacetate (DCA), bearing DMSO (cis-[Pt(DCA)2(Me2SO-S)2], 2) or phosphines (cis-[Pt(DCA)2(PPh3)(Me2SO-S)], 3, cis-[Pt(DCA)2(P)2], P = PPh33a, P = PTA 4a and [Pt(DCA)(P)3]DCA, P = PPh33b, P = PTA, 4b) as neutral ligands was prepared by a simple fast route from the inorganic synthon [PtCO3(Me2SO-S)2], 1. The X-ray crystal structures of 2, 3, 3a and 4a were determined. The antiproliferative activity of 2, 4a, and 4b was evaluated against two human cancer cell lines, cisplatin sensitive A2780 and cisplatin resistant SKOV-3, and the results were compared with known amine analogues and with the dichloride precursors
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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