In vitro phototoxicity of 5-aminolevulinic acid and its methyl ester and the influence of barrier properties on their release from a bioadhesive patch.

opical administration of excess exogenous 5-aminolevulinic acid (ALA) leads to selective accumulation of the potent photosensitiser protoporphyrin IX (PpIX) in neoplastic cells, which can then be destroyed by irradiation with visible light. Due to its hydrophilicity, ALA penetrates deep lesions, such as nodular basal cell carcinomas (BCCs) poorly. As a result, more lipophilic esters of ALA have been employed to improve tissue penetration. In this study, the in vitro release of ALA and M-ALA from proprietary creams and novel patch-based systems across normal stratum corneum and a model membrane designed to mimic the abnormal stratum corneum overlying neoplastic skin lesions were investigated. Receiver compartment drug concentrations were compared with the concentrations of each drug producing high levels of PpIX production and subsequent light-induced kill in a model neoplastic cell line (LOX). LOX cells were found to be quite resistant to ALA- and M-ALA-induced phototoxicity. However, drug concentrations achieved in receiver compartments were comparable to those required to induce high levels of cell death upon irradiation in cell lines reported in the literature. Patches released significantly less drug across normal stratum corneum and significantly more across the model membrane. This is of major significance since the selectivity of PDT for neoplastic lesions will be further enhanced by the delivery system. ALA/M-ALA will only be delivered in significant amounts to the abnormal tissue. PpIX will only then accumulate in the neoplastic cells and the normal surrounding tissue will be unharmed upon irradiation.

Social networks applied to training

In this article, we address the importance and relevance that social networks exhibit in their use as an educational resource.  This relevance relies in the possibility of implementing new learning resources or increasing the level of the participant's connectivity, as well as developing learning communities.  Also, the risk entailed from their use is discussed, especially for the students that have a low technological education or those having excessive confidence on the media.  It is important to highlight that the educational use of social networks is not a simple extension or translation of the student's habitual, recreational use, but that it implies an important change in the roles given to teachers as well as learners; from accommodative learning environments that only encourage memorization to other environments that demand an active, reflective, collaborative and proactive attitude, that require the development/acquisition of technological as well as social abilities, aptitudes and values.  It is also important to highlight that a correct implementation and adequate use will not only foment formal learning, but also informal and non-formal learning.

The effect of flexoelectricity on the dielectric properties of inhomogeneously strained ferroelectric thin films

Recent experimental measurements of large flexoelectric coefficients in ferroelectric ceramics suggest that strain gradients can affect the polarization and permittivity behaviour of inhomogeneously strained ferroelectrics. Here we present a phenomenological model of the effect of flexoelectricity on the dielectric constant, polarization, Curie temperature (T-C), temperature of maximum dielectric constant (T-m) and temperature of the onset of reversible polarization (T-ferro) for ferroelectric thin films subject to substrate-induced epitaxial strains that are allowed to relax with thickness, and the qualitative and quantitative predictions of the model are compared with experimental results for (Ba0.5Sr0.5)TiO3 thin films on SrRuO3 electrodes. It is shown that flexoelectricity can play an important role in decreasing the maximum dielectric constant of ferroelectric thin films under inhomogeneous in-plane strain, regardless of the sign of the strain gradient.

Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: potential for enhanced topical photodynamic therapy

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA). In this study, silicon microneedle arrays were used, for the first time, to enhance skin penetration of ALA in vitro and in vivo. Puncturing excised murine skin with 6x7 arrays of microneedles 270 mum in height, with a diameter of 240 mum at the base and an interspacing of 750 mum led to a significant increase in transdermal delivery of ALA released from a bioadhesive patch containing 19 mg ALA cm(-2). Microneedle puncture enhanced ALA delivery to the upper regions of excised porcine skin but, at mean depths of 1.875 mm, ALA concentrations were similar to control values, possibly reflecting binding of ALA by tissue components. However, and importantly, in vivo experiments using nude mice showed that microneedle puncture could reduce application time and ALA dose required to induce high levels of the photosensitiser protoporphyrin IX in skin. This clearly has implications for clinical practice, as shorter application times would mean improved patient and clinician convenience and also that more patients could be treated in the same session. As ALA is expensive and degrades rapidly via a second order reaction, reducing the required dose is also a notable advantage.

Environmental tolerances of free-living coralline algae (maerl): implications for European marine conservation

Maerl is a general term used for loose-lying subtidal beds of nodular coralline red algae. Maerl beds support high associated invertebrate and algal biodiversity, and are subject to European and UK conservation legislation. Previous investigations have shown European maerl to be ecologically fragile due to growth rates of approximately I mm per year. However, these very slow growth rates have hampered attempts to determine the key ecological requirements and sensitivity characteristics of living maerl. In this study, photosynthetic capacity determined by pulse amplitude modulated (PAM) fluorometry was used as a diagnostic of stress caused by various environmental conditions. Maerl species were exposed to a range of temperatures, salinities and light levels and to burial, fragmentation, desiccation and heavy metal treatment. Maerl was not as susceptible as previously assumed to extremes of salinity, temperature and heavy metal pollution, but burial, especially in fine or anoxic sediments, was lethal or caused significant stress. These data indicate that the main anthropogenic hazard for live maerl and the rich communities that depend on them is smothering by fine sediment, such as that produced by trawling or maerl extraction, from sewage discharges or shellfish and fish farm waste, and sedimentation resulting from disruption to tidal flow. (C) 2004 Elsevier Ltd. All rights reserved.

Influence of solution viscosity and injection protocol on distribution patterns of jet injectors: Application to photodynamic tumour targeting

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA) and preformed photosensitisers. In this study, we investigated the potential of jet injection to deliver both ALA and a preformed photosensitiser (meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate, TMP) into a defined volume of skin. Initial studies using a model hydrogel showed that as standoff distance is increased, injection depth decreases. As the ejected volume is increased, injection depth increases. It was also shown, for the first time, that, as injection solution viscosity was increased, for a given injection setting and standoff distance, both total depth of jet penetration, L-t, and depth at which the maximum width of the penetration pattern occurred, L-m, decreased progressively. For a standoff distance of zero, the maximum width of the penetration pattern, L-w, increased progressively with increasing viscosity at each of the injection settings. Conversely, when the standoff distance was 2.5 mm, L-w decreased progressively with increasing viscosity. Studies with neonate porcine skin revealed that an injection protocol comprising an 8.98 mPas solution, an arbitrary injection setting of 8 and a standoff distance of zero was capable of delivering photosensitisers to a volume of tissue (L-t of 2.91 mm, L-m of 2.14 mm, L-w of 5. 10 mm) comparable to that occupied by a typical nodular basal cell carcinoma. Both ALA and TMP were successfully delivered using jet injection, with peak tissue concentrations (67.3 mg cm(-3) and 5.6 mg cm(-3), respectively) achieved at a depth of around 1.0 mm and substantial reductions in drug concentration seen at depths below 3.0 mm. Consequently, jet injection may be suitable for selective targeting of ALA or preformed photosensitisers to skin tumours. (c) 2007 Elsevier B.V. All rights reserved.

Hexyl Aminolaevulinate Is a More Effective Topical Photosensitiser Precursor than Methyl Aminolaevulinate and 5-Aminolaevulinic Acids When Applied in Equimolar Doses

Aminolaevulinic acid (ALA) is known to poorly penetrate into thick lesions, such as nodular basal cell carcinomas Short chain ALA esters, possessing increased lipophilicity relative to their hydrophilic parent, have previously been shown to be highly efficient at inducing protoporphyrin IX (PpIX) production in cell culture, at equimolar concentrations. In contrast, in vitro skin permeation and in vivo animal studies, which up to now have compared prodrugs on a % w/vv basis, have failed to demonstrate such benefits For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into an o/w cream preparation. In vitro penetration studies into excised porcine skin revealed that increased levels of h-ALA, compared to ALA and m-ALA were found in the upper skin layers, at all drug loadings studied. Topical application of the formulations to nude murine skin in vivo, revealed that creams containing h-ALA induced significantly higher levels of peak PpIX fluorescence (F-max = 289.0) at low concentrations compared to m-ALA (F-max = 159.2) and ALA (F-max = 191 9). Importantly, this study indicates that when compared on an equimolar basis, h-ALA has improved skin penetration, leading to enhanced PpIX production compared to the parent drug and m-ALA (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3486-3498, 2010

Influence of penetration enhancers on topical delivery of 5-aminolevulinic acid from bioadhesive patches

Objectives The inclusion 01 chemical penetration enhancers in a novel patch-based system for the delivery of 5-aminolevulinic acid (ALA) was examined in vitro and in vivo. Poor penetration of ALA has been implicated as the primary factor for low response rates achieved with topical ALA-based photodynamic therapy of thicker neoplastic lesions. such as nodular basal cell carcinomas.

Deposit-feeding mechanisms and resource partitioning in tropical holothurians

Aspidochirote holothurians found on tropical reef flats feed on particulate deposits which form a variety of substrata. The synaptid holothurian Opheodesoma grisea (Semper) feeds in a similar manner by scraping deposits from the surfaces of sea grasses. Distributional and gut content analyses showed that species partitioning is on the basis of substratum and particle size preference. Scanning electron microscopy revealed that the tentacles of aspidochirotes have a nodular surface while those of O. grisea have a tessellated surface structure. The twelve different species examined were shown to have different tentacular surface textures which bore an apparent relationship with the mean particle sizes selected by the different species. Light microscope studies of tentacle sections confirmed earlier observations on the extent of the water vascular system in aspidochirote and pinnate tentacles. From these observations a functional interpretation is proposed for tentacular operation and the means of particle selection in such holothurians.

Laterite as a disinfectant.

A groundwater programme monitoring flow and quality of a potable water spring in a slum district in Kampala, Uganda revealed that although latrines acted as the principal means of organic waste disposal for the 1000 plus people living in the spring’s catchment, levels of faecal indicator bacteria (TVC 45 Deg C) in spring discharge remained at or below detection during the dry season, despite the presence of high levels of chloride (45mg/l-56mg/l) and nitrate (23mg/l – 30mg/l NO3-N), indicating sewage impacts. A programme of column and batch testing of laterite underlying the area provided a means of investigating the soil’s attenuation capacity under more controlled conditions.
X-ray diffraction analyses revealed the laterite to be dominated by quartz and kaolinite with minor (<5% by volume) quantities of haematite. Batch studies revealed that over 99% of bacteriophage adsorbed to haematite in less than 5 minutes. By contrast batch tests on haematite-free soil samples from the Blue Hills in Australia showed that although they had comparable dominant mineralogy and iron coverage on their surfaces (determined from Energy dispersive X-ray fluorescence) they had negligible ability to adsorb H40/1.
Based on the results of the batch studies using natural soils, a programme of batch studies, undertaken using pure haematite showed the mineral to have an extremely high capacity to adsorb bacteriophage, and suggested that it was responsible for the levels of attenuation observed.
The results of column studies were in keeping with the findings of batch experiments. Injection of 20 pore volumes of 300 pfu/mL of the bacteriophage H40/1 into a 20mm diameter glass column packed with sand sized (Ø>500µm) laterite revealed that the column could irreversibly remove over 2.5 log10 bacteriophage over its 10cm length.
Importance:
Mineralogical and batch test data provide convincing evidence to show that laterite can potentially act as an inexpensive means of removing micro organisms from water. The material, particularly in nodular form, displays considerable potential to act as an alternative filter material to conventional quartz filter sands.

Influence of a Single Grain Boundary on Domain Wall Motion in Ferroelectrics

Epitaxial tetragonal 425 and 611 nm thick Pb(ZrTi)O (PZT) films are deposited by pulsed laser deposition on SrRuO-coated (100) SrTiO 24° tilt angle bicrystal substrates to create a single PZT grain boundary with a well-defined orientation. On either side of the bicrystal boundary, the films show square hysteresis loops and have dielectric permittivities of 456 and 576, with loss tangents of 0.010 and 0.015, respectively. Using piezoresponse force microscopy (PFM), a decrease in the nonlinear piezoelectric response is observed in the vicinity (720-820 nm) of the grain boundary. This region represents the width over which the extrinsic contributions to the piezoelectric response (e.g., those associated with the domain density/configuration and/or the domain wall mobility) are influenced by the presence of the grain boundary. Transmission electron microscope (TEM) images collected near and far from the grain boundary indicate a strong preference for (101)/(1-01) type domain walls at the grain boundary, whereas (011)/(01-1) and (101)/(1-01) are observed away from this region. It is proposed that the elastic strain field at the grain boundary interacts with the ferro-electric/elastic domain structure, stabilizing (101)/(1-01) rather than (011)/(01-1) type domain walls, which inhibits domain wall motion under applied field and decreases non-linearity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES: Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Sequence stratigraphy related distribution of diagenetic alterations In Miocene deltaic and shoreface arenites, the Suez Rift, EGYPT.

The distribution of eogenetic alterations in shoreface-offshore and coarse-grained deltaic, calcarenite to hybrid arenites of the Mheiherrat Formation (lower Rudeis), Early Miocene, the Gulf of Suez, Egypt) can be constrained within a sequence stratigraphic framework. The bioclast-rich, shoreface (trangressive systems tract; TST) and shoreface (highstand systems tract; HST) arenites, particularly those below the parasequence boundaries and maximum flooding surface, are cemented by grain-coating microcrystalline, circumgranular isopacheous acicular and columnar, and coarse-crystalline calcite (δ18OVPDB = -3.6 to -0.3 ‰; δ13CVPDB = -2.3 to -0.7 ‰), non-Ferro an dolomite (δ18OVPDB = -3.9 to +0.9‰; δ13CVPDB = -2.5 ‰ to -0.7 ‰), and pyrite. Zeolite, palygorskite and gypsum occur in the HST shoreface arenites, being enhanced by aird climatic condations. The coarse-grained deltaic LST deposits are pervasively cemented by coarse-crystalline, pore-filling calcite and small amounts of microcrystalline calcite (δ18OVPDB = -4.4 to -2.3 ‰; δ13CVPDB = -2.8 to -1.3 ‰) and non-ferroan dolomite (δ18OVPDB = -4.8 to -2.5 ‰; δ13CVPDB = -3.3 to -1.5 ‰). Thus, this study demonstrates that changes in pore-water chemistry, which induced changes in the texture, composition and extent of cementation in the Miocene arenites was controlled by changes in the relative sea level and by the paleo-climatic conditions during deposition of the HST arenites.

Sequence stratigraphy related distribution of diagenetic alterations In Miocene deltaic and shoreface arenites, the Suez Rift, EGYPT.. Available from: https://www.researchgate.net/publication/264545153_Sequence_stratigraphy_related_distribution_of_diagenetic_alterations_In_Miocene_deltaic_and_shoreface_arenites_the_Suez_Rift_EGYPT [accessed Apr 15, 2015].

Valorização de resíduos industriais na formulação de produtos e pigmentos cerâmicos: processamento e desenvolvimento de cor

A valorização de diferentes resíduos industriais provenientes dosector de tratamento/revestimento de superfícies metálicas pode ser obtida utilizando-os como matérias-primas na formulação de pigmentos cerâmicos, sintetizados pelo método cerâmico convencional. Neste trabalho avaliou-se a viabilidade de incorporar lamas geradas pelos processos de (i) anodização, ricas em alumínio, (ii) de niquelagem e cromagem de torneiras, usadas como fonte de níquel e crómio, e (iii) da decapagem química de aços de uma trefilaria, ricas em ferro, utilizadas por si só, ou em conjunto com matérias-primas comerciais, para a obtenção depigmentos cerâmicos que coram, de forma estável, diversas matrizes cerâmicas e vítreas. Esta solução assegura ainda a inertização de potenciaisespécies perigosas presentes nos resíduos, resultando produtos inócuospara a saúde pública. Procedeu-se à caracterização de cada resíduo, em termos de composição química e mineralógica, comportamento térmico, grau de toxicidade, distribuição granulométrica, teor de humidade, etc. Verificou-se a constância das características das lamas, recorrendo à análise de lotes recolhidos em momentos distintos. Os resíduos são essencialmente constituídos por hidróxidos metálicos e foram utilizados após secagem e desagregação. No entanto, a lama de anodização de alumínio sofreu um tratamento térmico suplementar a 1400ºC. O método de síntese dos pigmentos englobou as seguintes etapas: (i) doseamento; (ii) homogeneização; (iii) calcinação; (iv) lavagem e moagem.Procedeu-se à caracterização dos pigmentos, avaliando a cor por espectroscopia de reflectância difusae pelo método CIELAB e determinando as características físico-químicas relevantes. Posteriormente, testou-se o seu desempenho em produtos cerâmicos distintos (corpos e vidrados), aferindo o desempenho cromático e a estabilidade. Numa primeira fase, desenvolveram-se e caracterizaram-se tipos distintos de pigmentos: (i) com base na estrutura do corundo (ii) verde Victória deuvarovite (iii) violeta de cassiterite com crómio (iv) pigmento carmim de malaiaíte; (v)pretos e castanhos com base na estrutura da espinela. Aprofundaram-se depois os estudos do pigmento carmim de malaiaítee do pigmento preto com base na estrutura da espinela. O pigmento carmim de malaiaíte, CaSnSiO5:Cr2O3, é formulado coma lama gerada no processo de niquelagem e cromagem. Avaliou-se a influência do teor de lama na temperatura de síntese e na qualidade cromática, em comparação com um pigmento formulado com reagentes puros. O pigmento preto com estrutura de espinela de níquel, crómio e ferro, foii formulado exclusivamente a partir das lamas geradas nos processos de cromagem/niquelagem e de decapagem química do aço. Avaliaram-se as características cromáticas e o grau de inertização dos elementos tóxicospresentes, em função da estequiometria e do tratamento térmico. Estudou-se ainda um novo sistema com base na estrutura da hibonite(CaAl12O19), que permite a obtenção de pigmentos azuis e que utiliza a lama de cromagem e niquelagem. As espécies cromóforas (Ni2+ ou Co2+) assumem coordenação tetraédrica quando substituem os iões Al3+ que ocupam as posições M5 da rede da hibonite. A formação simultânea de anortite permite reduzir a temperatura de síntese.Para além do carácter inovador deste pigmento de dissolução sólida, a qualidade cromática e a sua estabilidade são interessantes. Além disso, os teores de cobalto ou níquel são reduzidosrelativamente aos utilizados em formulações comerciais de pigmentos azuis, o que se traduz em importantes vantagens económicas e ambientais.

Properties of self-assembled diluted magnetic semiconductor nanostructures

Este trabalho centra-se na investigação da possibilidade de se conseguir um semicondutor magnético diluído (SMD) baseado em ZnO. Foi levado a cabo um estudo detalhado das propriedades magnéticas e estruturais de estruturas de ZnO, nomeadamente nanofios (NFs), nanocristais (NCs) e filmes finos, dopadas com metais de transição (MTs). Foram usadas várias técnicas experimentais para caracterizar estas estruturas, designadamente difracção de raios-X, microscopia electrónica de varrimento, ressonância magnética, SQUID, e medidas de transporte. Foram incorporados substitucionalmente nos sítios do Zn iões de Mn2+ e Co2+ em ambos os NFs e NCs de ZnO. Revelou-se para ambos os iões dopantes, que a incorporação é heterogénea, uma vez que parte do sinal de ressonância paramagnética electrónica (RPE) vem de iões de MTs em ambientes distorcidos ou enriquecidos com MTs. A partir das intensidades relativas dos espectros de RPE e de modificações da superfície, demonstra-se ainda que os NCs exibem uma estrutura core-shell. Os resultados, evidenciam que, com o aumento da concentração de MTs, a dimensão dos NCs diminui e aumentam as distorções da rede. Finalmente, no caso dos NCs dopados com Mn, obteve-se o resultado singular de que a espessura da shell é da ordem de 0.3 nm e de que existe uma acumulação de Mn na mesma. Com o objectivo de esclarecer o papel dos portadores de carga na medição das interacções ferromagnéticas, foram co-dopados filmes de ZnO com Mn e Al ou com Co e Al. Os filmes dopados com Mn, revelaram-se simplesmente paramagnéticos, com os iões de Mn substitucionais nos sítios do Zn. Por outro lado, os filmes dopados com Co exibem ferromagnetismo fraco não intrínseco, provavelmente devido a decomposição spinodal. Foram ainda efectuados estudos comparativos com filmes de ligas de Zn1-xFexO. Como era de esperar, detectaram-se segundas fases de espinela e de óxido de ferro nestas ligas; todas as amostras exibiam curvas de histerese a 300 K. Estes resultados suportam a hipótese de que as segundas fases são responsáveis pelo comportamento magnético observado em muitos sistemas baseados em ZnO. Não se observou nenhuma evidência de ferromagnetismo mediado por portadores de carga. As experiências mostram que a análise de RPE permite demonstrar directamente se e onde estão incorporados os iões de MTs e evidenciam a importância dos efeitos de superfície para dimensões menores que ~15 nm, para as quais se formam estruturas core-shell. As investigações realizadas no âmbito desta tese demonstram que nenhuma das amostras de ZnO estudadas exibiram propriedades de um SMD intrínseco e que, no futuro, são necessários estudos teóricos e experimentais detalhados das interacções de troca entre os iões de MTs e os átomos do ZnO para determinar a origem das propriedades magnéticas observadas.