bluuebunny/crossref_metadata_2025 huggingface dataset:
Effcient and Effective Automated Digital Hair
Removal from Dermoscopy Images
Authors: Koehoorn Joost , Sobiecki André , Rauber Paulo , Jalba Andrei , Telea Alexandru
Published: March 2016

We propose a method for digital hair removal from dermoscopic images, based on a threshold-set
model. For every threshold, we adapt a recent gap-detection algorithm to find hairs, and merge results in a
single mask image.We find hairs in this mask by combining morphological filters and medial descriptors.We
derive robust parameter values for our method from over 300 skin images.We detail a GPU implementation of
our method and show how it compares favorably with five existing hair removal methods, in terms of removing
both long and stubble hair of various colors, contrasts, and curvature. We also discuss qualitative and
quantitative validations of the produced hair-free images, and show how our method effectively addresses
the task of automatic skin-tumor segmentation for hair-occluded images.
Catalytic activity of Pd-Ni in the oxidation of hydrogen for the safety of nuclear power plant
Authors: Łomot Dariusz , Karpiński Zbigniew
Published: March 2016

Pd-Ni/Al2O3 systems were investigated in the reaction of hydrogen oxidation in terms of their possible application as catalysts used in passive autocatalytic recombiners (PARs) used in nuclear power plants. Testing experiments were carried out in a flowing system at different temperatures and humidity of the reaction mixture. The bimetallic catalysts exhibited higher response to the increase of temperature and higher resistance to inhibit water than the monometallic palladium catalyst. They showed excellent stability during a few tens of hours, similarly, like their monometallic counterpart. Our bimetallic catalysts of hydrogen oxidation can be used as cheaper alternatives to catalysts based on the precious metals in the hydrogen oxidation without loss of their activity over time.
Application of pyrolysis process in processing of mixed food wastes
Authors: Grycová Barbora , Koutník Ivan , Pryszcz Adrian , Kaloč Miroslav
Published: March 2016

The food industry produces large amounts of solid and also liquid wastes. Different waste materials and their mixtures were pyrolysed in the laboratory pyrolysis unit to a final temperature of 800°C with a 10 minute delay at the final temperature. After the pyrolysis process of the selected wastes a mass balance of the resulting products, off-line analysis of the pyrolysis gas and evaluation of solid and liquid products were carried out. The highest concentration of methane, hydrogen and carbon monoxide were analyzed during the 4th gas sampling at a temperature of approx. 720–780°C. The concentration of hydrogen was measured in the range from 22 to 40 vol.%. The resulting iodine numbers of samples CHFO, DS, DSFW reach values that indicate the possibility of using them to produce the so-called “disposable sorbents” in wastewater treatment. The WC condensate can be directed to further processing and upgrading for energy use.
Study of compounds emitted during thermo-oxidative decomposition of polyester fabrics
Authors: Dzięcioł Małgorzata , Huzar Elżbieta
Published: March 2016

Compounds emitted during thermo-oxidative decomposition of three commercial polyester fabrics for indoor outfit and decorations (upholstery, curtains) were studied. The experiments were carried out in a flow tubular furnace at 600°C in an air atmosphere. During decomposition process the complex mixtures of volatile and solid compounds were emitted. The main volatile products were carbon oxides, benzene, acetaldehyde, vinyl benzoate and acetophe-none. The emitted solid compounds consisted mainly of aromatic carboxylic acids and its derivatives, among which the greatest part took terephthalic acid, monovinyl terephthalate and benzoic acid. The small amounts of polycyclic aromatic hydrocarbons were also emitted. The emission profiles of the tested polyester fabrics were similar. The presence of toxic compounds indicates the possibility of serious hazard for people during fire.
Theoretical Holism in the Sociology of Development
Authors: Mahutga Matthew C
Published: March 2016

In this article, I apply Alderson and Nielsen's (1999) holistic approach to the sociology of development by revisiting the consequences of private markets and foreign direct investment (FDI) for earnings inequality during postsocialist transition. I begin by arguing that FDI increases the pace of private market expansion and thereby affects inequality through an indirect causal pathway unrecognized in the literature. The total effect of FDI thus depends in part on how private markets drive distributional change. I then introduce a maturation thesis to reconcile debates over the distributional consequences of private markets, where private markets first reduce and then increase inequality. If FDI increases the pace of private market expansion and if the distributional consequences of private markets increase as they expand, then FDI's total effect on inequality should grow with the expansion of private markets. Evidence drawn from a time-series crosssection regression analysis of earnings inequality among 18 transition countries supports this intervention. FDI increases the pace of private market expansion, and the effect of private markets changes from negative to positive as private markets expand. Thus the total effect of FDI increases with the size of the private market. I conclude by implicating these findings in debates about postsocialist transition and the sociology of development more generally.
Features of Structure Formation During the Thermal Synthesis of Powders Carbide-Steels from Waste Sludge of Bearing Steels
Authors: Bagliuk G.A. , Mamonova A.A. , Uskova N.O. , Bezdorozhev A.V.
Published: March 2016

The peculiarities of structure and phase composition of the briquettes material obtained by thermal fusion of the mixture consisting of a powder slurry obtained by grinding rollers and cone bearings, titanium hydride and graphite. It was shown that after synthesis at temperatures of 1150÷1200 0С phase composition of the obtained alloy includes mainly phases of titanium carbide, cementite and α-Fe. When boron carbide introduced into the mixture too, the last dissociates during thermal synthesis, resulting along with titanium carbide in the alloy significant content boride phases - TiB, TiB2, Ti2B5 and FeB was identified.
Metallization of Carbon Fibers by Double and Triple Copper Composition
Authors: Sirenko H.O. , Skladanyuk M.B. , Soltys L.M.
Published: March 2016

The theoretical foundations of physics and chemistry and application technology of single- and double-layer coating based on Cu0+Cu2O, Ni0+P, Pb0 on the surface of carbonated fibers have been reviewed. The changes of surface layers crystal structure of carbon fibres in the course of copper-plating have been investigated. The metallic coating process using modified formaldehyde and zinc technology was realized. It is established that copper content in copper – copper oxide increases when using two-layer alternately modified formaldehyde and zinc methods.
Insight into the interactive effects of β-glycerophosphate molecules on thermosensitive chitosan-based hydrogels
Authors: Rahmati Maryam , Samadikuchaksaraei Ali , Mozafari Masoud
Published: March 2016

The purpose of the present study was to provide insights into the interactive effects of β-glycerophosphate (β-GP) molecules on thermosensitive chitosan-based hydrogels, which experience sol–gel transformation around the physiological temperature. This study also investigated the influence of β-GP as a physical cross-linker and pH modifier on chitosan-based hydrogels by Fourier transform infrared spectroscopy with the aim of achieving a better understanding of the effect of β-GP action mechanism. For this purpose, some solutions with 2% (w/v) chitosan were mixed with different amounts of β-GP in the range of 0–20% (w/v) concentrations. It was shown that by further addition of β-GP, the anionic phosphate units of β-GP in combination with the cationic amine units of chitosan could provide electrostatic cross-linking for making chitosan-based hydrogels. All the β-GP–chitosan solutions remained at the physiological pH after complete mixing. In addition, the viability of 3T3 fibroblast cells determined by MTT assay and scanning suggested that the samples containing 12% β-GP would show optimum biological characteristics. This study demonstrated that the synthesized chitosan–β-GP is a biocompatible thermosensitive system, which can be potentially used for tissue engineering applications in different areas, such as cartilage injections, and that injectability and appropriate gelation behavior are important factors.
Non-uniform thermal strains and stresses in energy piles
Authors: Abdelaziz Sherif , Ozudogru Tolga Y.
Published: March 2016

This paper presents the non-uniform thermally induced strains and stresses that develop in the cross-sections of energy piles when subjected to operational energy demands. The thermal operation of energy piles depends on the thermal demands of the supported building. These thermal demands vary seasonally, daily and even hourly, which generates non-uniform temperature changes over the pile’s cross-section throughout the lifetime of the system. Therefore, non-uniform thermal strains and stresses develop over the cross-section of energy piles. Numerical analyses performed in this study indicate that the maximum temperature changes and the thermally induced strains and stresses occur near the location of the ground loops. Further, contradicting the current understanding that heating the piles creates only thermal compressive stresses, while cooling them creates only thermal tensile stresses; tensile and compressive thermal stresses were found to coexist during heating and cooling over the same pile cross-section due to the non-uniform temperature changes. Furthermore, the magnitude of the tensile stresses that develop due to non-uniform temperature changes is crucial when the reinforcing cage is cut short of the pile toe. Finally, ignoring the non-uniform temperature changes while processing the temperatures and strains measured in full-scale tests will result in errors in approximated thermal stresses.
Role of clay properties in improvement using small stone piles
Authors: Hari Gopinathan Pillai , Sankar Natesan , Chandrakaran Sridhar
Published: March 2016

Ground improvement using group floating stone compaction piles with a small replacement area ratio is an effective solution for improving soft clay for construction of buildings with up to two storeys. Sufficient data based on field studies for the improvement of the ground using stone compaction piles with a smaller diameter and low area replacement ratios are not available. This study was intended to create a database for assessing the improvement of clay ground and predicting the suitability of group floating compaction piles with granular materials for the improvement of clay ground based on the properties of clay. Twelve sites were selected for conducting the study. The effects of different soil properties such as sensitivity, liquidity index and consistency index on the improvement of the undrained shear strength of clay were investigated. Also, a correlation of standard penetration test values before and after the improvements was arrived at based on field observations. The results are discussed in this paper.
Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy
Authors: Qin Hua-Zhang , Zhang Ming-Chao , Le Wei-Bo , Ren Qiang , Chen Da-Cheng , Zeng Cai-Hong , Liu Lei , Zuo Ke , Xu Feng , Liu Zhi-Hong
Published: March 2016

Serum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb− (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb−/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.
The Role of Learning for Asset Prices, Business Cycles, and Monetary Policy
Authors: Winkler Fabian
Published: March 2016

The importance of financial frictions for the business cycle is widely recognized, but it is less recognized that their effects depend heavily on the underlying asset pricing theory. This paper examines the implications of learning-based asset pricing. I construct a model in which firms' ability to access credit depends on their market value, and investors rely on past observation to predict future stock prices. Agents' expectations remain model-consistent conditional on their beliefs about stock prices, which disciplines the expectation formation process. The model matches several asset price properties such as return volatility and predictability and also leads to a powerful feedback loop between asset prices and real activity, substantially amplifying business cycle shocks. Agents' expectational errors on asset prices spill over to forecasts of economic activity, resulting in forecast error predictability that closely matches survey data. A reaction of monetary policy to asset prices is welfare-improving under learning but not under rational expectations.
Factores topográficos y edáficos que influyen en la estructura de especies perennes de islas de la costa de Sinaloa, México
Authors: Sánchez Soto Bardo Heleodoro , García-Moya Edmundo , Reyes-Olivas Álvaro , Romero-Manzanares Angélica , Luna-Cavazos Mario
Published: March 2016

Cover data of 29 perennial species and 25 environmental variables, in 57 sites, were used to assess vegetation-environment relationships of 16 islands in the coast of Sinaloa, Mexico. The sites were classified through cluster analysis and ordered using detrended correspondence analysis (DCA), then ecological gradients were analyzed with canonical correspondence analysis (CCA). Correlations, species-environment, were significant (P< 0.05) to ten environmental variables. The first axis was related to nitrate (0.776) and pH (-0.584), while the second axis correlated with rocky cover (-0.901), soil depth (0.757), percentage of silt (-0.696), slope (-0.685), and percentage of sand (0.663). These variables were those that best explained the structure of the Sinaloa Island vegetation. The effect of such factors is noticeable between island groups: those with addition of seabird guano, islands with rocks of volcanic origin, and those of sandbar.
Estructura, heterogeneidad de estadios y patrón de dispersión espacial de Dioon holmgrenii (Zamiaceae)
Authors: Velasco García Mario Valerio , Valdez-Hernández Juan Ignacio , Ramírez-Herrera Carlos , Hernández-Hernández María Luisa , López-Upton Javier , López-Mata Lauro , López-Sánchez Higinio
Published: March 2016

The aims of this research were to determine the structure, heterogeneity of stages, and spatial dispersion pattern of ten populations of Dioon holmgrenii, an endangered species endemic to southern Oaxaca, for conservation purpose. Eleven and nine sampling units were established in conditions without apparent land use change and change in land use, respectively. The developed stages were identified in non-reproductive and reproductive plants, and inside each of them the development stages. The average density of individuals was higher in conditions without apparent land use change (782 plants ha1) than in change in land use (353 plants ha-1). High percentage of seedlings and adults was occurring in conditions without apparent land use, and low pre-reproductive and juveniles; however, high percentage of adults and low percentage of seedlings, saplings and pre-reproductive were found in condition change in land use. The heterogeneity of stages was higher (P= 0.048) under conditions without apparent land use change (H’ = 1.57) than with change in land use (H’ = 1.38). The similarity was higher in conditions without apparent land use change (IM-H= 0.93, ISCT= 0.81) and within change in land use (IM-H= 0.83, ISCT= 0.61) than among both conditions (IM-H= 0.70, ISCT= 0.53). The spatial dispersion pattern of individuals was primarily aggregate (65 %). Reproductive and non-reproductive individuals were distributed in aggregates 12 and 14 out of 20 sampling units, respectively. The results show that agriculture and grazing affect the structure, heterogeneity of stages and the spatial dispersion pattern; so these should be considered in the future management of populations.
Clima psicológico como preditor da saúde e do bem-estar de profissionais de saúde em contexto hospitalar
Authors: Carvalho Isabel Silva
Published: March 2016

O clima psicológico , enquanto representação psicológica do ambiente de trabalho, ou seja, das estruturas, processos e acontecimentos proximais (Rousseau, 188) e reflexo dos processos de atribuição de sentido às experiências de trabalho (Weick, 1995), tem sido considerado como uma variável explicativa importante do comportamento, saúde e bem-estar dos indivíduos nas organizações (Parker, Baltes, Young, Huff, Altmann, Lacoste & Roberts, 2003). Este estudo, com uma amostra de 375 profissionais de saúde hospitalar, tem como objectivo a análise da relação entre o clima psicológico a saúde e o bem-estar. Tem como nível de análise o indivíduo (Reichers e Schneider, 1990), e como referencial teórico o modelo de Jones & James (1979). A saúde e o bem-estar estão avaliados através da percepção da saúde física e psicológica, vitalidade e funcionamento cognitivo e social. Os resultados aplicam para o papel do clima psicológico enquanto preditor da saúde e bem-estar, bem como para o papel de mediação da satisfação com o trabalho nesta relação. São discutidas as implicações nas intervenções de saúde ocupacional cujo objectivo seja a melhoria da qualidade de vida no trabalho.DOI: http://dx.doi.org/10.17575/rpsicol.v21i1.355
Estou mais seguro na minha cidade do que os outros: identidade com o lugar e optimismo comparativo na percepção de riscos urbanos
Authors: Lima Maria Luísa , Marques Sibila , Batel Susana , Carvalho Sandra , Haldon Juana , Pornin Stephanie
Published: March 2016

Esta pesquisa pretendeu estudar o optimismo comparativo face aos riscos urbanos e explorar o papel que a identificação com a cidade de residência tem neste processo. O estudo foi realizado através de um inquérito a 156 estudantes universitários, residentes em Lisboa, Huelva e Lyon. Os resultados revelaram a existência de optimismo comparativo face a todos os riscos urbanos considerados (carteirismo, assalto da casa, terrorismo e queda de avião): os riscos para o próprio foram sempre considerados inferiores em relação aos riscos para os outros. No entanto,, os residentes consideraram-se menos vulneráveis do que os residentes de outras cidades (comparação exo-grupal) em particular no caso dos riscos graves e incontroláveis (terrorismo e queda de avião), sendo menos optimistas relativamente aos riscos menos graves e controláveis (assalto e carteirismo). Verificou-se que, no caso dos riscos urbanos incontroláveis, os inquiridos mais identificados com a sua cidade de residência revelam maior optimismo comparativo face aos residentes de outras cidades.DOI: http://dx.doi.org/10.17575/rpsicol.v21i2.366
Factores ambientais e psicossossiais da avaliação do risco de furto por carteirista: o caso de dois locais em Lisboa
Authors: Sautkina Elena , António Clara , Caseira Hugo , Correia Filipe , Dimitriou Dimitris , Grijó Cláudia , Loureiro Ana , Morais Rita
Published: March 2016

É do conhecimento comum que o furto por carteirista é um tipo de crime que se encontra em ambiente urbano. Baseada em factores ambientais e psicossociais de representações espaciais de segurança/insegurança, previamente identificados, e presente investigação pretendeu explorar como este tipo de factores podem afectar as avaliações das pessoas, no que se refere ao risco de serem assaltadas por carteirista. Neste sentido, foram considerados dois locais em Lisboa, diferindo principalmente nas suas características ambientais, físicas e sociais. Os resultados mostram que fortes ligações sociais num local podem revelar-se muito importantes para a avaliação do risco de furto por carteirista, afastando e tornando menos importante as características ambientais físicas, enquanto que, nos locais de maior heterogeneidade social, onde as ligações sociais são fracas, o ambiente físico torna-se consequentemente mais importante para as percepções de segurança.DOI: http://dx.doi.org/10.17575/rpsicol.v21i2.368
(Re)pensar os conflitos intragrupais: desempenho e níveis de desenvolvimento
Authors: Dinas Isabel Cristina Dórdio , Lourenço Paulo Renato , Miguez José
Published: March 2016

Contrariando as abordagens tradicionais do conflito intragrupal, que consideram este fenómeno negativo para o desempenho, as perspectivas mais recentes sublinham as suas potencialidades ao nível da inovação e da criatividade das equipas de trabalho. Os estudos empíricos desenvolvidos têm, no entanto, encontrado poucas evidências para a funcionalidade do conflito. O presente artigo procura contribuir para uma melhor compreensão das relações entre o conflito, as estratégias de gestão de conflitos e o desempenho grupal, por um lado, bem como da forma como os conflitos são vividos e geridos ao longo do desenvolvimento grupal, por outro. Participaram no nosso estudo 68 equipas de trabalho do departamento de produção de 8 organizações do sector industrial que desempenhavam tarefas com um baixo nível de complexidade. Os resultados revelaram que o conflito centrado no desenvolvimento de tarefas se relaciona negativamente com o desempenho e que a utilização de estratégias integrativas se assume como a única abordagem aos conflitos é diferente, ao longo do desenvolvimento grupal. Para testar o padrão de resultados encontrado, importa realizar novos estudos com equipas cujas tarefas requeiram uma elevada coordenação de esforços e remetam para resultados caracterizados por uma elevada imprevisibilidade.DOI: http://dx.doi.org/10.17575/rpsicol.v21i2.373
Contribuições da análise de discurso para a política pública de educação ambiental
Authors: Luca Andrea Quirino de , Lagazzi Suzy Maria
Published: March 2016

Resumo: Esse artigo tem como perspectiva teórico-metodológica a Análise de Discurso de linha materialista. Seu objetivo é buscar historicidade e lugares de significação de documentos referenciais da política pública federal de Educação Ambiental e, assim, trazer contribuições da análise de discurso para a área de saber da educação ambiental. Os documentos analisados são o Tratado de Educação Ambiental para Sociedades Sustentáveis e Responsabilidade Global, o Programa Nacional de Educação Ambiental (ProNEA), e o Programa de Formação de Educadoras(es) Ambientais: por um Brasil educado e educando ambientalmente para a sustentabilidade (ProFEA). Procuramos dar visibilidade aos pré-construídos e condições de produção que sustentam esse discurso, e terminamos o trabalho apontando quais noções materialistas podem contribuir com a discussão e apropriação dos documentos da política pública de educação ambiental pelos coletivos que se relacionam com essa política.Palavras-chave: Educação Ambiental; Política Pública de Educação Ambiental; Análise de Discurso.Abstract: This article uses the materialistic conception of the Discourse Analysis as a theoretical and methodological perspective, based on authors such as Michel Pêcheux, Louis Althusser and Eni Orlandi, who are the authors that make up the conceptual framework of this field. The main goal of this article is to seek historicity and significance in federal documents of public policy for Environmental Education, thus bringing the discourse analysis to contribute to the area of environmental knowledge and education. The documents analyzed are the Treaty of Environmental Education for Sustainable Societies and Global Responsibility, the National Environmental Education Program (ProNEA), and the Environmental Educator Training Program: for an educated Brazil and educating for environmental sustainability (ProFEA). We have tried to give visibility to the pre-built and production conditions that sustain these discourses, and finished our work pointing out which materialistic notions can contribute to the discussion and appropriation of public policy documents on environmental education for groups that relate to this policy. Major brands and regularities found dealing with freedom and autonomy, and the contributions made relate to the notion of decentralization of the subject to understand how the discursive process takes place and its effects on production of subjectivity so as to affirm that the subject is not the source of his own speech.Keywords: Environmental Education; Public Policy on Environmental Education; Discourse Analysis.
The water use efficiency of maize depending on abiotic stress factors in field experiments
Authors: Csajbók József , Kutasy Erika , Pepó Péter
Published: March 2016

There is little direct information about the effects of the abiotic stress factors such as low soil water content on the photosynthesis system of field crops. Some recent publications pay attention to this field of research. Water stress has significant effect on the yield and other agronomic parameters of maize. The aim of our work was to get more data about the relations between water supply and the assimilation parameters. The photosynthetic gas exchange parameters of maize are remarkably improved by nutrient supply in well watered conditions. The water stress through decreased stomatal conductance has significant negative effect on the assimilation parameters of the crops. The obtained results suggest that the water use efficiency of the maize is higher in dry conditions. In well water supply state maize uses up to 300 per cent more water for 1 g CO2 assimilation.
New results of nutrient utilization and response of maize (Zea mays L.) hybrids
Authors: Pepó Péter , Karancsi Lajos Gábor
Published: March 2016

In a long-term experiment, the fertilizer response of 10 maize hybrids of different genotypes was studied on chernozem soil in a favourable year. The yields of the hybrids varied between 9500 and 18600 kg ha-1 depending upon the fertilizer treatment and the genotype. The excellent nutrient and water management of the chernozem soil was proved by the high yield (9500 – 14600 kg ha-1) obtained in the control. Even in such a good soil, the maize hybrids demanded fertilization and responded to it with a high yield increasement (3200 – 6500 kg ha-1). From among the tested hybrids, 8 hybrids gave the highest yield in the N120+PK treatment, while 2 hybrids reached their maximum yield in the N150+PK fertilizer treatment (13500 – 18600 kg ha-1 depending upon the hybrid). The water utilization of maize was improved as a result of the optimum fertilization. The water-use efficiency (WUE) was 30.35 kg mm-1, while it increased to 42.22 kg mm-1 at the optimum fertilizer dosage (N120+PK). The natural nutrient utilization ability (yield in the control treatment) and the yield obtained at the optimum fertilizer dosage (N120+PK and N150+PK) were used in a special coordinate system.
Evidencia alapú gondolkodás az ifjúsági munkában: Transnational Cooperation Activity programok „On the spot” online survey néhány eredménye
Authors: Szombathelyi Szilvia
Published: March 2016

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Tomka Béla: Szociálpolitika Fejlődés, formák, összehasonlítások
Authors: Czibere Ibolya , Vadász Gabriella
Published: March 2016

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Effect of Inflammation on Molecular Targets and Drug Transporters
Authors: Hanafy Sherif , El-Kadi Ayman O.S. , Jamali Fakhreddin
Published: March 2016

Inflammation, the host’s response to infection and injury, is associated with altered expression of genes such as metabolizing enzymes, transporters, receptors and plasma proteins. The purpose of the present work was to characterize the effect of inflammation on selected molecular targets and transporters that affect drugs’ action and disposition. We have used rats with adjuvant arthritis (AA), an animal model of chronic inflammation. The AA group received 0.2 ml of 50 mg ml-1 Mycobacterium butyricum suspended in squalene into the tail base. On day 12, the rats were euthanized and their organs (heart, liver, kidneys and intestine) excised. Expression of Cav1.2, β1-AR, β2-AR, α1A-AR, Nav1.2, Nav1.6, Kv1.5, Kv2.1, Kv3.1, oatp1a1, oatp1a5, oatp1b2, oatp2b1, oatp4a1, oat2, oat3, oct1, mdr1a, bsep, mrp1, mrp3, mrp6, IL-1α, IFN-γ, iNOS, MCP-1, IL-10, Cox-1 and Cox-2 were determined by real time polymerase chain reaction (RT-PCR). Inflammation resulted in a significant reduction of oct1, oatp4a1 and mrp1 gene expression in the liver and oatp2b1, mrp6 and bsep gene expression in the kidney. Oatp4a1 and mdr1a were found to be significantly upregulated in rat heart. In conclusion, inflammation alters the gene expression of some mediators and drug transporters that can influence the behavior of drugs in the body and contribute to therapeutic failure.

This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Application of Caco-2 Cell Line in Herb-Drug Interaction Studies: Current Approaches and Challenges
Authors: Awortwe Charles , Fasinu P.S. , Rosenkranz B.
Published: March 2016

The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Rheological Investigation of Self-emulsification Process
Authors: Biradar Shailesh V , Dhumal Ravindra S , Paradkar Anant
Published: March 2016

PURPOSE

Aim of this study is to investigate the mechanism of self-emulsification through rheological analysis of intermediate liquid crystalline (LC) phase formed during self-emulsification process.

METHODS

Binary system of tween 80 (T80) and imwitor 742 (I742) was used and different SES were prepared with I742 at 10, 30, 50, 70 and 90% w/w concentration levels. Self-emulsification was monitored by visual observations and droplet size measurement. Mesophases obtained by 50% v/v hydration of SES were utilized for polarizing microscopy, differential scanning calorimetry and rheological studies.

RESULTS

Good emulsification with nano sized droplets was observed for SES 30% as compared to micron sized droplets for other SES. In polarizing microscopy, formation of intermediate LC phase was observed in all SES. Lamellar phase was evident in 30% SES while other SES exhibited micellar cubic phase. Presence of high level of structurally bound water in thermal analysis confirmed mesophase formation in all SES. In frequency sweep, decrease in elastic modulus, and an increase in phase degree and loss tangent was observed for 30% SES. Exactly opposite trend was seen in other SES. Thus, rheological studies concluded presence of weak and fragile mesophase structure in 30% SES while LC phase structure with little structural buildup was observed in other SES. This weak mesosphere structure in SES 30% presented no or very little resistance against strain induced deformation. Therefore, during emulsification, weak mesophase in SES 30% ruptured with ease and released jet of nanosize droplets compared to coarse droplets for other SES.

CONCLUSION

This study signifies the effect of viscoelastic properties of intermediate LC phase on self-emulsification performance.
Randomised, Double-Blind, Placebo-Controlled Study of a Single Dose of an Amylmetacresol/2,4-dichlorobenzyl Alcohol Plus Lidocaine Lozenge or a Hexylresorcinol Lozenge for the Treatment of Acute Sore Throat Due to Upper Respiratory Tract Infection
Authors: McNally Damien , Shephard Adrian , Field Emma
Published: March 2016

Purpose: Sore throat is a frequent reason for seeking medical care but few prescription options are available. Lozenges are effective in delivering active ingredients to the throat. This study was conducted to determine the analgesic efficacy of two lozenges  one containing amylmetacresol (AMC)/2,4-dichlorobenzyl alcohol (DCBA) and lidocaine and one containing hexylresorcinol  versus placebo in patients with acute sore throat due to upper respiratory tract infection (URTI). Methods: This was a multicentre, randomised, double-blind, parallel group, placebo-controlled study. In total, 190 patients were randomised 1:1:1 to a single dose of AMC/DCBA + lidocaine, hexylresorcinol or placebo lozenge. Subjective ratings of throat soreness, difficulty swallowing, swollen throat, numbing, and sore throat relief were obtained up to 2 hours post dose. Patient and investigator global ratings and a consumer questionnaire were also collected. The primary endpoint was the change from baseline in severity of throat soreness for both lozenges versus placebo at 2 hours post dose. Results: The hexylresorcinol lozenge demonstrated superiority over placebo for primary and secondary efficacy variables including those related to throat soreness, sore throat relief and difficulty swallowing; the AMC/DCBA + lidocaine lozenge was also superior to placebo for secondary endpoints at various time points but did not reach significance for the primary efficacy variable. Both lozenges had a rapid onset of action from 1–10 minutes post dose for the AMC/DCBA + lidocaine lozenge and 1–5 minutes post dose for the hexylresorcinol lozenge. Numbness was reported from 1 minute post dose with the AMC/DCBA + lidocaine lozenge and was greatest at 15 minutes. Numbness was reported from 5 minutes post dose with the hexylresorcinol lozenge and was greatest at 10 minutes. Both lozenges were well tolerated. Conclusions: Both AMC/DCBA + lidocaine and hexylresorcinol lozenges provided rapid and effective sore throat relief in patients with URTI.

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A New Vesicle-loaded Hydrogel System Suitable for Topical Applications: Preparation and Characterization
Authors: Carafa Maria , Marianecci Carlotta , Di Marzio Luisa , Rinaldi Federica , Di Meo Chiara , Matricardi Pietro , Alhaique Franco , Coviello Tommasina
Published: March 2016

ABSTRACT – Purpose. Aim of this research was to prepare and study drug release from a new formulation consisting of non ionic surfactant vesicular structures, niosomes (NSVs), loaded with model molecules calcein (CALC), nile red (NR), ibuprofen (IBU) or caffeine (CAFF), and embedded in a hydrogel matrix. Methods. The system locust bean gum/xanthan (1:1), prepared at 60 °C, was used to entrap the vesicles (Tween 20/cholesterol 1:1), loaded with guest molecules and the release profiles were detected at 32 °C. The hydrogel systems were characterized by means of scanning electron microscopy; niosomes were characterized by means of size and -potential measurements. Results. Size measurements showed that a slight increase in vesicle dimensions occurs after inclusion of CALC or CAFF (hydrophilic molecules) in the vesicular structures. -potential measurements showed that the inclusion of these molecules did not significantly modify the surface charge of empty vesicles. This was probably related to an almost negligible drug adsorption on the vesicle surface. The release from the niosomes-gel systems of two probes (CALC and NR) showed that the diffusion of CALC through the gel was not affected by the niosome entrapment while for NR, the presence of vesicles was crucial. The release profiles from niosomes-gel systems and from the hydrogel alone of model drugs, CAFF and IBU, showed an appreciable difference between the two drugs: the more hydrophilic CAFF was released much faster than IBU. In all release studies turbidity, dimension and -potential analyses indicated that the loaded niosomes were released by the hydrogel matrix without being damaged. Conclusions. The reported in vitro experiments show the capability of the novel formulation to combine the qualities of both chosen single systems, i.e. the niosomes and the polymeric network. The hydrogel shows a protective effect on vesicle integrity and leads to a slow release of the loaded model molecules from the polysaccharidic system.

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Dissolution Enhancement of Gliclazide Using pH Change Approach in Presence of Twelve Stabilizers with Various Physico-Chemical Properties
Authors: Talari Roya , Nokhodchi Ali , Mostafavi Seyed Abolfazl , Varshosaz Jaleh
Published: March 2016

Purpose: The micronization using milling process to enhance dissolution rate is extremely inefficient due to a high energy input, and disruptions in the crystal lattice which can cause physical or chemical instability. Therefore, the aim of the present study is to use in situ micronization process through pH change method to produce micron-size gliclazide particles for fast dissolution hence better bioavailability. Methods: Gliclazide was recrystallized in presence of 12 different stabilizers and the effects of each stabilizer on micromeritic behaviors, morphology of microcrystals, dissolution rate and solid state of recrystallized drug particles were investigated. Results: The results showed that recrystallized samples showed faster dissolution rate than untreated gliclazide particles and the fastest dissolution rate was observed for the samples recrystallized in presence of PEG 1500. Some of the recrystallized drug samples in presence of stabilizers dissolved 100% within the first 5 min showing at least 10 times greater dissolution rate than the dissolution rate of untreated gliclazide powders. Micromeritic studies showed that in situ micronization technique via pH change method is able to produce smaller particle size with a high surface area. The results also showed that the type of stabilizer had significant impact on morphology of recrystallized drug particles. The untreated gliclazide is rod or rectangular shape, whereas the crystals produced in presence of stabilizers, depending on the type of stabilizer, were very fine particles with irregular, cubic, rectangular, granular and spherical/modular shape. The results showed that crystallization of gliclazide in presence of stabilizers reduced the crystallinity of the samples as confirmed by XRPD and DSC results. Conclusion: In situ micronization of gliclazide through pH change method can successfully be used to produce micron-sized drug particles to enhance dissolution rate.
Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.
Authors: Kurosaki Tomoaki , Kitahara Takashi , Teshima Mugen , Nishida Koyo , Nakamura Junzo , Nakashima Mikiro , To Hideto , Hukuchi Hiromitsu , Hamamoto Tomoyuki , Sasaki Hitoshi
Published: March 2016

Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.
In vitro Characterization of the Oxidation of a Pyridinium Metabolite of Haloperidol by Human Placenta: The Effect of Smoking
Authors: Fang Jim , Song Jiuxue
Published: March 2016

Purpose. The antipsychotic drug haloperidol can be metabolised to pyridinium metabolites haloperidol pyridinium (HP+) and reduced haloperidol pyridinium (RHP+). These pyridinium metabolites were proposed to contribute to the extrapyramidal side effects of haloperidol, because they are structural analogues of N-methyl-4-phenylpyridinium (MPP+), a well-known neurotoxin. RHP+ can be oxidized to HP+ by CYP1A1. In the current study, the oxidation of RHP+ to HP+ was investigated using human placenta microsomal preparations which contain relatively high levels of CYP1A1. Methods. Cytochrome P450 isoenzymes responsible for the metabolism of RHP+ were characterized in vitro using human placenta microsomal preparations from smokers and non-smokers. Results. A comparison of the metabolic activities between smokers and non-smokers suggests that smokers had higher activities for the oxidation of RHP+. A selective antibody against CYP1A1 was a partial inhibitor of RHP+ oxidase in placenta from smokers but had no effect in placenta from non-smokers. Furafylline and ketokonazole were shown to be stronger inhibitors of the oxidation of RHP+ to HP+ in liver than in placenta. This seems to indicate important contributions of CYP1A1 and CYP3A7 as compared to CYP1A2 and CYP3A4, respectively, because furafylline and ketokonazole are stronger inhibitors of CYP1A2 and CYP3A4 than CYP1A1 and CYP3A7, respectively. Interestingly, α-naphathoflavone enhanced the metabolic activity in liver microsomes due to its activator effect on CYP3A4. On the other hand, α-naphathoflavone partially inhibited the activity in placenta microsomes, indicating a role played by CYP1A1 or CYP1A2 in the oxidation of RHP+ in placenta. Conclusions. These data indicate that CYP1A1 plays an important role in the oxidation of RHP+ to HP+ in placenta from smokers. CYP3A7 and CYP3A4 could also play important roles in the metabolism of RHP+ in placenta microsomes.

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Statins Use and Risk of Breast Cancer Recurrence and Death: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Mansourian Marjan , Haghjooy-Javanmard Shaghayegh , Eshraghi Azadeh , Vaseghi Golnaz , Hayatshahi Alireza , Thomas Jean
Published: March 2016

Purpose. Statins are widely prescribed drugs for lowering cholesterol. Some studies have suggested that statins can prevent breast cancer recurrence and reduce mortality rate. However they are not conclusive. Present systematic review and meta-analysis of published cohort studies was conducted to determine the effects of statins intake and risk of breast cancer recurrence and mortality rate. Methods. Online databases (PubMed, Embase, Scopus, EBSCO and Cochrane Collaboration) were searched through October 2014. Pooled relative risks and 95 % confidence intervals were calculated with random-effects. Results. A total of 8 cohort studies (4 for recurrence 2 for mortality and 2 for both) involving 124669 participants with breast cancer were eligible. Our results suggest a significant reduction in  recurrence (OR= 0.79. I2= 38%) and death (OR = 0.84, I2 = 8.58 %) among statin users. Conclusion. Our meta-analysis suggests that breast cancer patients will benefit from statin intake, however from these cohorts we are unable to differentiate between various statins in terms of effectiveness and duration of use. We highly propose conducting randomized clinical trials. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
Determination of Metformin in Human Plasma and Urine by High-Performance Liquid Chromatography Using Small Sample Volume and Conventional Octadecyl Silane Column
Authors: Brocks Dion , Gabr Raniah Q. , Padwal Raj S.
Published: March 2016

Purpose: To develop a selective and sensitive high-performance liquid chromatographic method for the determination of metformin in human plasma and urine, using a conventional reverse phase column and low specimen volume. Methods: Extraction of metformin and ranitidine (as internal standard) from plasma and urine samples (100 µL) was performed with a 1-butanol-hexane (50:50, v/v) mixture under alkaline conditions followed by back-extraction into diluted acetic acid. Chromatography was carried out using a C18 column (250 mm×4.6 mm, 5 μm). A mobile phase consisting of acetonitrile and KH2PO4 (34:66, v/v) and sodium dodecyl sulphate (3 mM) was pumped at an isocratic flow rate of 0.7 mL/min. Results: The calibration curves were linear (>0.995) in the concentration ranges of 10–5000 and 2–2000 μg/mL for metformin in plasma and urine respectively. The mean absolute recoveries for 100 and 1000 ng/mL metformin in plasma using the present extraction procedure were 93.7 and 88.5%, respectively. The intra- and inter-day coefficients of variation in plasma and urine were