Oral administration of iron-saturated bovine lactoferrin-loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

We determined the anticancer efficacy and internalization mechanism of our polymeric-ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts.

What is the most effective way of increasing the bioavailability of dietary long chain omega-3 fatty acids-daily vs. weekly administration of fish oil?

The recommendations on the intake of long chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA) vary from eating oily fish ("once to twice per week") to consuming specified daily amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ("250-500 mg per day"). It is not known if there is a difference in the uptake/bioavailability between regular daily consumption of supplementsvs. consuming fish once or twice per week. In this study, the bioavailability of a daily dose of n-3 LC-PUFA (Constant treatment), representing supplements, vs. a large weekly dose of n-3 LC-PUFA (Spike treatment), representing consuming once or twice per week, was assessed. Six-week old healthy male Sprague-Dawley rats were fed either a Constant treatment, a Spike treatment or Control treatment (no n-3 LC-PUFA), for six weeks. The whole body, tissues and faeces were analysed for fatty acid content. The results showed that the major metabolic fate of the n-3 LC-PUFA (EPA+docosapentaenoic acid (DPA) + DHA) was towards catabolism (β-oxidation) accounting for over 70% of total dietary intake, whereas deposition accounted less than 25% of total dietary intake. It was found that significantly more n-3 LC-PUFA were β-oxidised when originating from the Constant treatment (84% of dose), compared with the Spike treatment (75% of dose). Conversely, it was found that significantly more n-3 LC-PUFA were deposited when originating from the Spike treatment (23% of dose), than from the Constant treatment (15% of dose). These unexpected findings show that a large dose of n-3 LC-PUFA once per week is more effective in increasing whole body n-3 LC-PUFA content in rats compared with a smaller dose delivered daily.

Global democratic theory: a critical introduction

Global Democratic Theory is the first comprehensive introduction to the changing contours of democracy in today’s hyperconnected world. Accessibly written for readers new to the topic, it considers the impact of globalization and global forms of governance and activism on democratic politics and examines how democratic theory has responded to address these challenges, including calls for new forms of democracy to be developed beyond the nation-state and for greater public participation and accountability in existing global institutions. Divided into two parts, the book shows how globalization provides both new obstacles and new opportunities for democracy. Part I explores the shifts underway at the national and international levels that are challenging democracy within nation-states around the world. In response, new proposals for global and transnational democracy have emerged. Part II critically analyses five main approaches of ‘global democratic theory’ Ð liberal internationalism, cosmopolitan democracy, deliberative democracy, social democracy and radical democracy, focusing on their specific interpretation of the problems facing democracy, their normative claims, and the feasibility of their proposed pathways of democratization. The book’s extensive account of the problems and possibilities facing democracy today will be essential reading for students and scholars of politics, political theory and political philosophy.

Institutional processes and the production of gender inequalities: the case of Australian child support research and administration

This article analyses the administrative and research capture of child support data as a case study of how institutional data collection processes are performative in perpetuating gendered inequalities. We compare interviews with 19 low-income single mothers and their longitudinal survey responses from the same research to reveal how low-income women strategically or inadvertently ‘smoothed’ their experiences when responding to data collection processes. This directly resulted in material and symbolic costs in the form of reduced welfare benefits and limited evidence with which to lobby for policy reform. These processes in turn provided benefits to fathers and the state in the form of reduced child support liabilities and enforcement action, and welfare outlays, respectively. We conclude that current administrative and research data collection practices provide a limited and gendered evidence base for administrative justice and policy reform.

Simmel, the police form and the limits of democratic policing

© 2015 The Author. I argue that the social theory of Georg Simmel can be used to illustrate certain limitations to the potential of democratic policing. Simmel makes a number of claims about trust, secrecy and accountability that are shown to have immediate relevance to my empirical case study of police-public consultation forums in Edinburgh, Scotland. Two particular aspects of the 'form' of the police-public relationship-the police's command of non-negotiable force and inequality in the reciprocity of information-play a key role in limiting some of the principal aspirations of democratic policing theory. There are permanent barriers to improving the democratic credentials of the police I argue, yet positive and progressive change is still achievable.

The role of middle class in democratic diffusion

The modernization hypothesis and the democratic domino theory have been at the forefront in explaining the democratization around the globe. This paper empirically investigates the ‘middle class-driven modernization’ hypothesis and the ‘middle class-driven democratic domino’ effect in a panel of 145 countries over the period 1985 to 2013. Using several middle class measures and a dynamic panel estimator, we show that the ‘middle class-driven modernization’ hypothesis finds strong empirical support in the sample of developing countries excluding Eastern Europe and Central Asia, while the ‘middle class-driven democratic domino’ effect finds support in the sample of developing countries excluding East Asia and the Pacific

Materials Collection Creation and Administration: A New Role for Libraries (White Paper)

The Problem/Opportunity: To define, identify, and guide design-based materials collections in academic settings and foster community among those with existing collections and/or those considering creating and supporting one. Contents and topics: What is a materials collection? Why have a materials collection? Acquisition strategies Organizational approaches Programming possibilities Symposium summary Resources

Mudanças institucionais, receitas cumulativas do governo federal e exportações no Brasil entre 1982 e 2001

Desde o início dos anos oitenta, o governo federal brasileiro passou a substituir a receitas de impostos tradicionais por receita de contribuições sociais (cumulativas) na composição da sua receita total (mudança de gestão). Alega-se que este procedimento é uma conseqüência das regras de compartilhamento estabelecidas (receitas de impostos do governo federal são compartilhadas com estados e municípios enquanto que receitas de contribuição não o são).Existem argumentos na literatura mostrando que este processo de descentralização das receitas teve sua origem na mudança de regime político (militar para democrático), outros com a nova Constituição de 1988 e, por último, outros afirmando que ele só foi possível porque a ineficiência das contribuições foi encoberta pela ineficiência alocativa da inflação. Por outro lado, fatos ocorridos no mesmo período, embora não citados na literatura, poderiam explicar ou ajudar na explicação deste comportamento. Entre eles, a fragmentação do poder executivo a partir de 1989 com a primeira eleição presidencial e/ou o processo de abertura da economia a partir dos anos noventa. Usando a técnica de OLS, observou-se que a Nova Constituição e a abertura da economia explicariam esta mudança de gestão. De qualquer forma, independente do que esteja explicando esta mudança, ela é apontada como altamente prejudicial a competitividade das exportações brasileiras. Existem várias proxies tentando medir este efeito, nenhuma delas considerando uma medida de gestão. Resolvemos realizar esta tentativa. Como tínhamos desconfiança da exogeneidade da variável representativa da abertura da economia no teste anterior, tratamos a questão com o instrumental de séries de tempo. No longo prazo, descobrimos que a mudança de gestão afeta negativamente as exportações e positivamente a abertura da economia por ser menos punitiva com as importações em termos de competitividade (as contribuições incidem apenas na comercialização dos produtos importados). JEL classification: H27; H77, H87.

Construção do estado e administração pública: uma abordagem histórica

Este trabalho visa analisar as etapas da formação do Estado moderno, desde o Estado Absoluto até o Estado Social-Democrático, e relacioná-las com as formas correspondentes de organização e administração do aparelho do Estado que culminam na reforma da gestão pública.

Master in Bussiness Administration (MBA) versus Mestrado Profissionalizante em Administração (MPA): diferenças e similaridades

This study had for objective to identify the similarities and differences between Executives Programs (Mestrado Modalidade Profissional) and Master in Business Administration (MBAs), specializations lato sensu. In order to achieve these objectives bibliographical and field researches were developed. The bibliographical research allowed to identify the uprising contradiction between Executive Education and Academic Education. The field research allowed to verify the differences and concrete similarities perceived by pupils and coordinators. In the field, interviews in depth and applied half-structuralized questionnaires had been carried through. The interviews had been taken the effect with the coordinators of the MBA courses and Mestrado Profissional/Executivo of five institutions. The half-structuralized questionnaires had been applied in two institutions, in the pupils of the groups of Mestrado Profissional/Executivo and MBA. The results of the interviews and of the questionnaires had been enclosed in one of the six categories previously defined in the study. The research corroborated the initial assumption, that detaches the differences between the cited courses.

Administração pública federal: propostas para o fortalecimento do controle sobre os atos praticados e o respectivo combate à corrupção

The characteristics of the Brazilian historic context, under which the predominant social relations have developed, have led to a process of income concentration and to the political power of the dominant classes. The slavery abolishment hasn't guaranteed the people the rights secured to privileged citizens in general. Such practices were observed during historic process as the low level literacy shown by the census of 1920, the political domination of oligarchies and the military coup, all as determining factors in process of political power concentration. The social indicators and the corruption are extremely unfavorable to our country, but we wonder if that happens only in underdeveloped societies. It is possible that even the American society, even the most developed societies, under the democratic capitalism, can suffer negative consequences of some corruption in the capitalism system. Our observations have led to the perception that all democratic society must be regulated by the State in order to preserve the stability of the system. It has also been observed that it is necessary more effective popular participation in order to neutralize economic groups¿ pressure. It has also become evident the necessity of reduction of commissioned office in the federal public administration. And, finally, it is fundamental to propose an amendment to the construction that allows the Public Ministry to have access to any bank, fiscal or telephonic information of anyone that is in office: It should be called "The Law of Moral Transparency". Those proposals will only be possible if there is massive popular participation and we hope that they express our people¿s will in order to appose to those who act only to obtain private benefits.