Industry perspective on a holistic container closure integrity approach to parenteral combination products.

Biologics are being developed more and more as parenteral combination products with drug delivery devices. The maintenance of sterility is imperative for such medical devices throughout their life cycle. Therefore, the container closure integrity (CCI) should, preferably, be built into the overall process, and not just demonstrated during the final testing of the combination product. The integrity is an important Critical Quality Attribute (CQA) and in the scope of specific considerations and studies during the combination product life cycle i.e., design robustness, assembly processes, storage (to end of shelf life), and shipping prior to patient use. The goal of this paper is to summarize an industry holistic approach to ensure CCI, for a combination product, and to build a scientifically based justification that Quality (in terms of CCI) is built into the overall process. Current analytical approaches used for characterization or Good Manufacturing Practice (GMP) CCI testing during combination product development will be described. However, the use of quality by design (QbD) during product development can reduce or eliminate routine batch level or stability testing of the combination product.

Os “dramas” de J. L. Moreno e a filosofia da diferença / Los “dramas” de J. L. Moreno y la filosofía de la diferencia / The J. L. Moreno's “dramas” and the philosophy of difference

O objetivo deste ensaio teórico é avançar no deslocamento dos "dramas" de Jacob Levy Moreno de uma política representacional para uma política da diferença. Metodologicamente, desenvolve uma análise conceitual e uma crítica institucional, a partir das filosofias da diferença de Michel Foucault, Gilles Deleuze e Félix Guattari. Questionam-se os projetos e a orientação das práticas pelos conceitos de psicoterapia, existência, identidade e liberdade. A gênese social dos dispositivos morenianos é abordada no sentido de elucidar a formação dos impasses relativos a tais projetos e práticas. Conclui-se que as potências do falso funcionam como eixo problemático com vistas a promover o deslocamento objetivado.(AU)

El objetivo de este ensayo teórico es avanzar en el desplazamiento de los "dramas" de Jacob Levy Moreno desde una política de representación para una política de la diferencia. Metodológicamente, desarrolla un análisis conceptual y una crítica institucional, a partir de las filosofías de la diferencia de Michel Foucault, Gilles Deleuze y Félix Guattari. Cuestiona los proyectos y la orientación práctica de los conceptos de psicoterapia, existencia, identidad y libertad. La génesis social de los dispositivos morenianos se discute con el fin de elucidar la formación de puntos muertos en estos proyectos y prácticas. De ello se desprende que las potencias de lo falso funcionan como eje problemático para promover el desplazamiento objetivado.(AU)

The aim of this paper is to advance the theoretical displacement of Jacob Levy Moreno "dramas" from a representational politics to a politics of difference. Methodologically, it develops a conceptual analysis and an institutional critique, from the philosophies of the difference of Michel Foucault, Gilles Deleuze and Félix Guattari. The projects and the practical orientation by the concepts of psychotherapy, existence, identity and freedom are questioned. The social genesis of morenian devices is approached in order to elucidate the formation of impasses on these projects and practices. It is concluded that the powers of the false function as a problematic axis to promote the displacement objectified.(AU)

Os “dramas” de J. L. Moreno e a filosofia da diferença / Los “dramas” de J. L. Moreno y la filosofía de la diferencia / The J. L. Moreno's “dramas” and the philosophy of difference

O objetivo deste ensaio teórico é avançar no deslocamento dos "dramas" de Jacob Levy Moreno de uma política representacional para uma política da diferença. Metodologicamente, desenvolve uma análise conceitual e uma crítica institucional, a partir das filosofias da diferença de Michel Foucault, Gilles Deleuze e Félix Guattari. Questionam-se os projetos e a orientação das práticas pelos conceitos de psicoterapia, existência, identidade e liberdade. A gênese social dos dispositivos morenianos é abordada no sentido de elucidar a formação dos impasses relativos a tais projetos e práticas. Conclui-se que as potências do falso funcionam como eixo problemático com vistas a promover o deslocamento objetivado.

El objetivo de este ensayo teórico es avanzar en el desplazamiento de los "dramas" de Jacob Levy Moreno desde una política de representación para una política de la diferencia. Metodológicamente, desarrolla un análisis conceptual y una crítica institucional, a partir de las filosofías de la diferencia de Michel Foucault, Gilles Deleuze y Félix Guattari. Cuestiona los proyectos y la orientación práctica de los conceptos de psicoterapia, existencia, identidad y libertad. La génesis social de los dispositivos morenianos se discute con el fin de elucidar la formación de puntos muertos en estos proyectos y prácticas. De ello se desprende que las potencias de lo falso funcionan como eje problemático para promover el desplazamiento objetivado.

The aim of this paper is to advance the theoretical displacement of Jacob Levy Moreno "dramas" from a representational politics to a politics of difference. Methodologically, it develops a conceptual analysis and an institutional critique, from the philosophies of the difference of Michel Foucault, Gilles Deleuze and Félix Guattari. The projects and the practical orientation by the concepts of psychotherapy, existence, identity and freedom are questioned. The social genesis of morenian devices is approached in order to elucidate the formation of impasses on these projects and practices. It is concluded that the powers of the false function as a problematic axis to promote the displacement objectified.

Judicialização da vida e penas e medidas alternativas: composições, tensionamentos, problematizações / Legalization of life and sentences and alternative measures: compositions, tensioning, problematizations

O objetivo deste artigo foi considerar a "Judicialização da Vida", analisando as práticas que dão suporte a este fenômeno, assim como seus efeitos sobre os modos de vida de pessoas que estão em contato direto com a justiça, cumprindo penas ou medidas alternativas (PMAs). Para tanto,usou-se como metodologia o diário de campo contendo a vivência dos autores no curso de formação em Direitos Humanos para pessoas que cumprem PMAs, além de cinco entrevistas semiestruturadas com os integrantes do referido curso. Com base na Arqueogenealogia de Foucault, buscou-se encontrar as práticas que são construídas, as verdades afirmadas, as instituições acionadas, etc. Observa-se, assim, a judicialização como um fenômeno complexo, que compreende o fácil acesso ao judiciário, o que possibilita solicitar sua intervenção em nossas vidas, além de valorizar a cultura punitiva, fazendo de nós juízes cotidianos. (AU)

The aim of this article was to consider the "Legalization of Life" by examining the practices that support this phenomenon, as well as its effects on the lifestyle of people who are in direct contact with the justice system, serving Alternative Measures Programs (AMPs). In order to do so, the methodology used was the research diary, containing the authors’ experience on the Human Rights course for people serving AMPs, as well as five semi-structured interviews with members of that course. Based on the Archeogenealogy by Foucault, there was an effort to identify the built practices, the truth stated, the institutions used and so on. Therefore, the judicialization is seen as a complex phenomenon that includes easy access to the judiciary, what allows requesting its intervention in our lives, as well as appreciating the punitive culture, making us every day judges. (AU)

Judicialização da vida e penas e medidasalternativas: composições, tensionamentos, problematizações / Legalization of life and sentences and alternative measures: compositions, tensioning, problematizations

O objetivo deste artigo foi considerar a "Judicialização da Vida", analisandoas práticas que dão suporte a este fenômeno, assim como seus efeitossobre os modos de vida de pessoas que estão em contato direto com a justiça, cumprindo penas ou medidas alternativas (PMAs). Para tanto,usou-se como metodologia o diário de campo contendo a vivência dos autores no curso de formação em Direitos Humanos para pessoas que cumprem PMAs, além de cinco entrevistas semiestruturadas com os integrantes do referido curso. Com base na Arqueogenealogia de Foucault,buscou-se encontrar as práticas que são construídas, as verdades afirmadas, as instituições acionadas, etc. Observa-se, assim, a judicialização como um fenômeno complexo, que compreende o fácil acesso ao judiciário, o que possibilita solicitar sua intervenção em nossas vidas, além de valorizar a cultura punitiva, fazendo de nós juízes cotidianos...

The aim of this article was to consider the "Legalization of Life" by examining the practices that support this phenomenon, as well as its effectson the lifestyle of people who are in direct contact with the justice system,serving Alternative Measures Programs (AMPs). In order to do so, themethodology used was the research diary, containing the authors’ experience on the Human Rights course for people serving AMPs, as well asfive semi-structured interviews with members of that course. Based on theArcheogenealogy by Foucault, there was an effort to identify the built practices, the truth stated, the institutions used and so on. Therefore, the judicialization is seen as a complex phenomenon that includes easy access to the judiciary, what allows requesting its intervention in our lives, as well as appreciating the punitive culture, making us every day judges...

Penas e medidas alternativas: ética como caminho / Alternative penalties end measures: ethics as a way / Penas y medidas alternativas: la ética como un camino

A Vara de Execuções de Penas e Medidas Alternativas da Grande Vitória (ES) vem utilizando um Curso de Educação em Direitos Humanos como maneira de seus munícipes cumprirem penas e medidas alternativas (PMAs), com um projeto intitulado “Exercendo Cidadania”. Dessa forma, por meio de uma pesquisa-intervenção, acompanhamos o projeto, analisando como se efetuam as PMAs na região, visando conhecer as práticas existentes e os efeitos do seu cumprimento sobre os modos de vida dos beneficiários. Utilizamos, como metodologia, vivências no curso, diários de campo e entrevistas com cinco apenados. Os dados foram analisados por meio da análise arqueogenealógica. Como resultado, percebemos o curso ora como um espaço de intensa troca de experiências, no qual a ética era o elemento norteador das discussões; ora um espaço onde a moralização de comportamentos e formas de vida era priorizada, não restando espaço para a reflexão.(AU)

The Court of Criminal Enforcement and Alternative Measure from Grande Vitória (ES) has been giving a course on Human Rights Education as a way to make its citizens serve the alternative penalties and measures (APM) through a project entitled “Exercising Citizenship”. Thus, through an intervention-research, it was possible to keep up with Project, analyzing how the APMs are executed in the region, aiming to know the existing practices and the effects of the compliance on the beneficiaries’ ways of life. As a methodology, it was used the life experiences in the course, field journals and interviews with five convicted. Data was analyzed based on the archeogenealogy analysis. As a result, the course was pointed out sometimes as a space of intense experience exchanging, where ethics was the key element of discussions, and ometimes as a space where the moralization of behaviors and living ways were prioritized, without any space for reflection.(AU)

La Rama, juzgado, vara de Ejecuciones de Penas y Medidas Alternativas de la ciudad de Vitória (ES) está utilizando un curso de educación en derechos humanos para que sus ciudadanos cumplan penas y medidas alternativas (PMAs), con un proyecto intitulado “Ejerciendo Ciudadanía”. De esa forma, por medio de una investigación-intervención, acompañamos el proyecto, analizando como se efectúan las PMAs en la región, con vistas a conocer las prácticas existentes y los efectos de su cumplimiento sobre los modos de vida de los beneficiarios. Utilizamos como metodología vivencias en el curso, diarios de campo y entrevistas a cinco detenidos. Los datos fueron analizados por medio del análisis arqueogenealógico . Como resultado, vimos el curso ora como un espacio de intenso cambio de experiencias, en el que la ética era el elemento rector de las discusiones; ora como un espacio en el que la moralización de comportamientos y formas de vida eran priorizados, no quedando espacio para la reflexión.(AU)

A potência instituinte no projeto "Exercendo Cidadania" / The instituting power in the project "Exercising Citizenship" / La potencia instituyente en el proyecto "Ejerciendo la Ciudadanía"

As Penas e Medidas Alternativas (PMAs) são cada vez mais utilizadas pelo sistema jurídico brasileiro. Diante desse contexto, a Vara de Execuções de Penas e Medidas Alternativas do Espírito Santo estabeleceu um convênio com Prefeitura Municipal de Vitória que oferece um curso de formação em Direitos Humanos, intitulado "Exercendo Cidadania" como forma de cumprimento das PMAs. Este artigo é resultado da análise preliminar de uma pesquisa que tem como objetivo analisar a execução das PMAs no município de Vitória-ES, com atenção especial para o curso em questão. O diário de campo foi o principal instrumento metodológico, confeccionado pelas vivências no curso de outubro a novembro de 2010. Ficamos atentos aos movimentos que nos indicavam como o apenado entende/vive/pensa a PMA,observando as formas rígidas, instituídas de efetivação das mesmas, mas também - e isso que tentamos dar visibilidade - a potência instituinte do curso.(AU)

The Penalties and Alternative measures (PAMs) are increasingly used by the Brazilian judiciary system. Given this context, the Sentencing Court of Execution and Alternative Penalties of the Espírito Santo State has established a partnership with the Vitória city hall that offers a training course on Human Rights entitled "Exercising Citizenship" as a way to accomplish the PAMs. This article is the result of a preliminary analysis of a research aiming at analyzing the performance of PAMs in Vitória, with special attention to this training course. The field diary was the main methodological tool, made from experiences in this course from October to November 2010. We were aware of the movements that indicated how the convicted understands / lives / thinks about the PMA, observing the rigid forms, instituted by the execution of the measures, but also - and this is what we try to give visibility - the instituting power of the course.(AU)

Las Penas y Medidas Alternativas (PMAs) son cada vez más utilizadas por el sistema jurídico brasileño. En este contexto, el Tribunal de Ejecución de Penas y Medidas Alternativas del Espírito Santo ha establecido un acuerdo con el Ayuntamiento de la ciudad de Vitória, que ofrece un curso de capacitación sobre Derechos Humanos titulado "Ejerciendo la Ciudadanía" como una manera de cumplir con las PMAs. Este artículo es el resultado de un análisis preliminar de una investigación que tiene como objetivo analizar el desempeño de las PMAs en la ciudad de Vitória, con especial atención al curso en cuestión. El diario de campo fue la principal herramienta metodológica, hecho a partir de experiencias en el curso de octubre a noviembre de 2010. Nos pusimos atentos a los movimientos que nos indicaban cómo el apenado entiende/vive/piensa la PMA, observando las formas rígidas, instituidas de realización de las mismas, pero también - y fue a eso que tratamos de dar visibilidad - la potencia instituyente del curso..(AU)

A potência instituinte no projeto "Exercendo Cidadania" / The instituting power in the project "Exercising Citizenship" / La potencia instituyente en el proyecto "Ejerciendo la Ciudadanía"

As Penas e Medidas Alternativas (PMAs) são cada vez mais utilizadas pelo sistema jurídico brasileiro. Diante desse contexto, a Vara de Execuções de Penas e Medidas Alternativas do Espírito Santo estabeleceu um convênio com Prefeitura Municipal de Vitória que oferece um curso de formação em Direitos Humanos, intitulado "Exercendo Cidadania" como forma de cumprimento das PMAs. Este artigo é resultado da análise preliminar de uma pesquisa que tem como objetivo analisar a execução das PMAs no município de Vitória-ES, com atenção especial para o curso em questão. O diário de campo foi o principal instrumento metodológico, confeccionado pelas vivências no curso de outubro a novembro de 2010. Ficamos atentos aos movimentos que nos indicavam como o apenado entende/vive/pensa a PMA,observando as formas rígidas, instituídas de efetivação das mesmas, mas também - e isso que tentamos dar visibilidade - a potência instituinte do curso.

The Penalties and Alternative measures (PAMs) are increasingly used by the Brazilian judiciary system. Given this context, the Sentencing Court of Execution and Alternative Penalties of the Espírito Santo State has established a partnership with the Vitória city hall that offers a training course on Human Rights entitled "Exercising Citizenship" as a way to accomplish the PAMs. This article is the result of a preliminary analysis of a research aiming at analyzing the performance of PAMs in Vitória, with special attention to this training course. The field diary was the main methodological tool, made from experiences in this course from October to November 2010. We were aware of the movements that indicated how the convicted understands / lives / thinks about the PMA, observing the rigid forms, instituted by the execution of the measures, but also - and this is what we try to give visibility - the instituting power of the course.

Las Penas y Medidas Alternativas (PMAs) son cada vez más utilizadas por el sistema jurídico brasileño. En este contexto, el Tribunal de Ejecución de Penas y Medidas Alternativas del Espírito Santo ha establecido un acuerdo con el Ayuntamiento de la ciudad de Vitória, que ofrece un curso de capacitación sobre Derechos Humanos titulado "Ejerciendo la Ciudadanía" como una manera de cumplir con las PMAs. Este artículo es el resultado de un análisis preliminar de una investigación que tiene como objetivo analizar el desempeño de las PMAs en la ciudad de Vitória, con especial atención al curso en cuestión. El diario de campo fue la principal herramienta metodológica, hecho a partir de experiencias en el curso de octubre a noviembre de 2010. Nos pusimos atentos a los movimientos que nos indicaban cómo el apenado entiende/vive/piensa la PMA, observando las formas rígidas, instituidas de realización de las mismas, pero también - y fue a eso que tratamos de dar visibilidad - la potencia instituyente del curso..

P(HPMA)-block-P(LA) copolymers in paclitaxel formulations: polylactide stereochemistry controls micellization, cellular uptake kinetics, intracellular localization and drug efficiency.

In order to explore the influence of polymer microstructure and stereochemistry in biological settings, the synthesis, micellization, cellular fate and the use in paclitaxel formulations of poly(N-(2-hydroxypropyl)-methacrylamide)-block-poly(L-lactide) (P(HPMA)-block-P(LLA)) and poly(N-(2-hydroxypropyl)-methacrylamide)-block-poly(DL-lactide) block copolymers (P(HPMA)-block-P(DLLA)) were studied. To this end, P(HPMA)-block-P(lactide) block copolymers and their fluorescently labeled analogues were synthesized. The polymers exhibited molecular weights M(n) around 20,000 g/mol with dispersities (D=M(w)/M(n)) below 1.3. In addition, the solution conformation of this new type of partially degradable amphiphilic block copolymers was studied with and without paclitaxel loading in PBS buffer (pH 7.2), employing fluorescence correlation spectroscopy (FCS). We observed polymeric micelles with a hydrodynamic diameter of 17.0 nm for a fluorescently labeled P(HPMA)-block-P(LLA) block copolymer (P2*) and 20.4 nm for a P(HPMA)-block-P(DLLA) block copolymer (P3*). For the corresponding loaded block copolymers aggregates with a diameter of 40.0 nm (P2*) and 41.4 nm (P3*) in formulations containing 17 wt.% paclitaxel were observed, respectively. While the block copolymer itself showed non-toxic behavior up to a concentration of 3 mg/mL in HeLa (human cervix adenocarcinoma) cells, the paclitaxel containing formulations showed IC 50 values in the range of 10-100 nM. The P(HPMA)-block-P(DLLA) polymer (P3*) enters the cells more efficiently than stereo regular polymer (P2*) via an energy-dependent uptake mechanism. Thus, differences in the IC(50) value are--most likely--attributed to significant changes in cellular uptake. Polymer tacticity and stereoregularity appear to represent a key feature determining cellular uptake and efficiency for the PLA block copolymer drug formulations. This work demonstrates the importance of the microstructure of polymers used in drug delivery systems (DDS).

Mulheres ciganas: medo, relações intergrupais e confrontos identitários / Gypsy Women: Fear, intergroup relations and identity conflicts

Através da Teoria da Identidade Social procurou-se conhecer os estereótipos presentes no imaginário rural associados ao grupo cigano, bem como os sentimentos associados a esta etnia. Foram entrevistadas 10 mulheres não-ciganas, moradoras de uma comunidade rural brasileira. Realizou-se a organização dos dados através do software ALCESTE. A análise das informações nos permitiu identificar o sentimento de medo como importante orientador das práticas relacionadas aos ciganos, confirmando características presentes no imaginário social amplamente difundido acerca desta etnia. Estão presentes os clássicos estereótipos de ladrões, malfeitores e amaldiçoados. Discute-se a dinâmica identitária provocada pelo conflito entre a comunidade rural e os ciganos, enfatizando os processos que orientam o campo de identificação e diferenciação endo/exogrupal.

Through the Theory of Social Identity our objective was to know the stereotypes present in the rural imaginary related to the gypsy group, and the feelings associated with this ethnic group. Ten women, non-gypsies, residents of a rural Brazilian community, participated in this study. We analyzed the data through the ALCESTE software. The analysis of the information obtained has allowed us to identify the feeling of fear as the main mediator of practices related to the gypsies, confirming characteristics widely present in the social imaginary about this ethnic group. There are present the classic stereotypes of thieves, criminals and the cursed. It discusses the dynamics of identity provoked by the conflict between the rural community and the gypsies, emphasizing the processes that guide the field of identification and differentiation in/out-group.

Polymer--drug conjugates as nano-sized medicines.

Polymer Therapeutics have enormously evolved in the past decades. Several polymeric drugs as well as polymer-protein conjugates have been in the market since the 90s, but although polymer-drug conjugates are already in clinical trials they still need to reach this final goal. There are four main convergent strategies to move this platform technology further. First, exploitation of new molecular targets in cancer therapy and design of polymer-drug conjugates as treatments for other diseases. Second, the development of combination therapy. Third, attempts to improve polymer chemistry, including the use of new well-defined architectures and the optimization of the advanced characterization techniques essential to transform a promising conjugate into a candidate for clinical evaluation. Finally, increased understanding of polymer conjugate features that govern clinical risk-benefit is leading to an appreciation of clinical biomarkers that will open new possibilities for personalized therapy.

Synthesis and in vitro evaluation of defined HPMA folate conjugates: influence of aggregation on folate receptor (FR) mediated cellular uptake.

In this article we report the synthesis and in vitro evaluation of well-defined, folate functionalized and fluorescently labeled polymers based on the clinically approved N-(2-hydroxypropyl)-methacrylamide (HPMA). The polymers were prepared applying the RAFT polymerization method as well as the reactive ester approach. The molecular weights of the polymers synthesized were around 15 and 30 kDa. The total content of conjugated folate varied from 0, 5, and 10 mol %. The cellular uptake of these polymers was investigated in the folate receptor (FR)-positive human nasopharyngeal epidermal carcinoma (KB-3-1) and FR-negative human lung epithelial carcinoma (A549) cancer cell lines. In FR-positive cells, the cellular uptake of polymers depended strongly on the folate content. The conjugates with the highest folate content led to the highest level of cell-associated fluorescence. Regarding influence of molecular weight, nonsignificant differences were observed when total cell uptake was analyzed. The cellular uptake is related to the aggregate formation of the polymer conjugates, which were studied by fluorescence correlation spectroscopy (FCS). For the conjugates, we found aggregates with a diameter ranging from 11-18 nm. Much to our surprise, we found aggregates of the same size for the 30 kDa polymer bearing 5 mol % folate and for the 15 and 30 kDa conjugates with a folate content of 10 mol %. Consequently, a different conformation in solution for the different conjugates was expected. By live cell confocal fluorescence microscopy the receptor-mediated endocytosis process was observed, as colocalization with lysosomal markers was achieved. In addition, cellular uptake was not observed in FR-negative cells (A549) and can be dramatically reduced by blocking the FR with free folic acid. Our findings clearly underline the need for a minimum amount of accessible folate units to target the FR that triggers specific cellular uptake. Furthermore, it has been demonstrated that the targeting vector itself strongly influences the aggregation behavior in solution and thus determines the interaction with cells regarding cellular uptake as well as intracellular localization.

Polymer-drug conjugates for novel molecular targets.

Polymer therapeutics can be already considered as a promising field in the human healthcare context. The discovery of the enhanced permeability and retention effect by Maeda, together with the modular model for the polymer-drug conjugate proposed by Ringsdorf, directed the early steps of polymer therapeutics towards cancer therapy. Orthodox anticancer drugs were preferentially chosen in the development of the first conjugates. The fast evolution of polymer chemistry and bioconjugation techniques, and a deeper understanding of cell biology has opened up exciting new challenges and opportunities. Four main directions have to be considered to develop this 'platform technology' further: the control of the synthetic process, the exhaustive characterization of the conjugate architectures, the conquest of combination therapy and the disclosure of new therapeutic targets. We illustrate in this article the exciting approaches offered by polymer-drug conjugates beyond classical cancer therapy, focusing on new, more effective and selective targets in cancer and in their use as treatments for other major human diseases.

Relevance of folic acid/polymer ratio in targeted PEG-epirubicin conjugates.

A series of PEG-epirubicin conjugates with different folic acid contents per polymer chain was synthesized in order to study the influence of polymer/targeting moiety ratio on selective cytotoxicity, cellular uptake and intracellular localization. Analogous carboxyl-terminated conjugates without folic acid were studied as control. The heterobifunctional HO-PEG-COOH was used as polymeric carrier, allowing the synthesis of conjugates with a good control over the chemical structure and the drug/polymer and polymer/targeting residue ratios. A dendron structure was synthesized at one end of the PEG chain with the aim to increase the number of folic acid molecules. L-2-aminoadipic acid was used as branching unit. The conjugates showed high stability under several physiological conditions. Biological evaluation was carried out in A549, HeLa and KB-3-1 human cell lines, as these cells have different levels of folate receptor (FR) expression. In particular A549 cells are FR negative (FR-), HeLa cells are FR positive (FR+) and KB-3-1 cells over-express FR (FR++). It was clearly shown that the biological activity of the conjugates was influenced by the presence and the number of folic acid molecules per polymer chain and by the level of FR expression on cell surface. Conjugates conformation in solution was also studied, as differences in size might well affect cell internalization. In the cell viability assay, conjugates without folic acid were unexpectedly more cytotoxic than the targeted conjugates, but their IC(50) values were similar in the three cell lines. Differently, the anti-proliferative activity of targeted derivatives markedly increased going from FR(-) to FR(++) cells. FACS and confocal microscopy studies showed greater cellular internalization with the targeted conjugates than with their non-targeted analogues; more importantly, this relationship is clearly dependent on folic acid content in the conjugates and FR expression level in the cell line used.

Gadjés em tendas Calons: um estudo exploratório com grupos ciganos semi-nômades em território capixaba / Gadjés in Calon tents: an exploratory study with semi-nomadic gypsie groups on a capixaba territory

A despeito da presença cigana no Brasil desde o século XVI, o conhecimento acerca do seu modo de vida é ainda insipiente. A literatura revela que as práticas sociais dirigidas ao povo cigano são pautadas em fortes estigmas relacionados a uma identidade considerada estranha e perigosa. O presente estudo descreve os processos identitários vinculados a um grupo da etnia Calon que busca a valorização de sua cultura e práticas endogrupais, reafirmando características que consideram positivas, de modo a compensar os estereótipos fortemente negativos que lhes são atribuídos. Verificou-se que a identidade cigana se sustenta nas estratégias de resistência criadas pelo grupo para que seus membros se reconheçam como parte da cultura cigana em constante confronto com as culturas não-ciganas (AU)

e about their way of life is still insipient. Literature shows that social practices aimed at the gypsy people are based on strong stigmas related to an identity considered strange and dangerous. The present study describes the identity processes related to a group of the Calon ethnicity that seeks the promotion of their culture and their group practices, reaffirming characteristics that they consider positive, in order to offset the very negative stereotypes attributed to them. It was found that the gypsy identity is sustained through strategies of resistance created by the group for its members to recognize themselves as part of the gypsy culture in constant confrontation with the non-gypsy cultures (AU)

Gadjés em tendas Calons: um estudo exploratório com grupos ciganos semi-nômades em território capixaba / Gadjés in Calon tents: an exploratory study with semi-nomadic gypsie groups on a capixaba territory

A despeito da presença cigana no Brasil desde o século XVI, o conhecimento acerca do seu modo de vida é ainda insipiente. A literatura revela que as práticas sociais dirigidas ao povo cigano são pautadas em fortes estigmas relacionados a uma identidade considerada estranha e perigosa. O presente estudo descreve os processos identitários vinculados a um grupo da etnia Calon que busca a valorização de sua cultura e práticas endogrupais, reafirmando características que consideram positivas, de modo a compensar os estereótipos fortemente negativos que lhes são atribuídos. Verificou-se que a identidade cigana se sustenta nas estratégias de resistência criadas pelo grupo para que seus membros se reconheçam como parte da cultura cigana em constante confronto com as culturas não-ciganas.

e about their way of life is still insipient. Literature shows that social practices aimed at the gypsy people are based on strong stigmas related to an identity considered strange and dangerous. The present study describes the identity processes related to a group of the Calon ethnicity that seeks the promotion of their culture and their group practices, reaffirming characteristics that they consider positive, in order to offset the very negative stereotypes attributed to them. It was found that the gypsy identity is sustained through strategies of resistance created by the group for its members to recognize themselves as part of the gypsy culture in constant confrontation with the non-gypsy cultures.

Synthesis, Characterization and Preliminary Biological Evaluation of P(HPMA)-b-P(LLA) Copolymers: A New Type of Functional Biocompatible Block Copolymer.

We describe a synthetic pathway to functional P(HPMA)-b-P(LLA) block copolymers. The synthesis relies on a combination of ring-opening polymerization of L-lactide, conversion into a chain transfer agent (CTA) for the RAFT polymerization of pentafluorophenyl methacrylate. A series of block copolymers was prepared that exhibited molecular weights $\overline M _{\rm n}$ ranging from 7 600 to 34 300 g · mol(-1) , with moderate PDI between 1.3 and 1.45. These reactive precursor polymers have been transformed into biocompatible P(HPMA)-b-P(LLA) copolymers and their fluorescently labeled derivatives by facile replacement of the pentafluorophenyl groups. The fluorescence label attached to this new type of a partially degradable amphiphilic block copolymer was used to study cellular uptake in human cervix adenocarcinoma (HeLa) cells as well as aggregation behavior by fluorescence correlation spectroscopy (FCS).

Processos identitários entre ciganos: da exclusão a uma cultura de liberdade / Identity processes among the gypsy people: from exclusion to a culture of freedom

Este estudio tuvo por objetivo saber como hombres y mujeres gitanas construyen su identidad étnica a través de las relaciones establecidas entre esta comunidad y grupos no-gitanos. Para ello, participaron de la investigación 07 hombres y 10 mujeres gitanas. Se realizaron entrevistas individuales con un guión semi-estructurado y se hizo el análisis de los datos por medio del software ALCESTE y del análisis del contenido. Los resultados demostraron que la cultura gitana posee aspectos singulares, con dos pilares aparentemente fundamentales para su estructuración - relaciones parentales y relaciones de género. Al dinamizar esas dimensiones, encontramos otras características importantes, como creencias religiosas, respeto por los ancianos, fidelidad en los acuerdos realizados y control de la virginidad femenina hasta el matrimonio.

This study aimed to know how gypsy men and women produce their ethnic identity through the relationship they establish between their community and the non-gypsy world. For that, 07 gypsy men and 10 gypsy women participated in this research. Individual interviews have been carried out with semistructured script and the data analysis was done using the software ALCESTE and the Content Analysis. The results have demonstrated that the gypsy culture has singular aspects, with two apparently fundamental pillars for their structuring - parental relationship and gender subjects. Applying dynamics to those dimensions, we find other important themes in the organization of this ethnic group, like religious beliefs, respect to the elderly, fidelity to the agreements and control of the female virginity until marriage.

Este estudo objetivou conhecer como homens e mulheres ciganos constroem sua identidade étnica através das relações estabelecidas entre essa comunidade e grupos não-ciganos. Participaram da pesquisa 07 homens e 10 mulheres ciganas. Foram realizadas entrevistas individuais com roteiro semiestruturado e procedeu-se a análise dos dados através do software ALCESTE e da Análise de Conteúdo. Os resultados demonstraram que a cultura cigana possui aspectos singulares, com dois pilares aparentemente fundamentais para sua estruturação - relações parentais e relações de gênero. Dinamizando essas dimensões, encontramos outras características importantes, como crenças religiosas, respeito aos mais velhos, fidelidade aos acordos firmados e controle da virgindade feminina até o casamento.

Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid.

Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC), is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by short plasma half-life, rapid metabolism and low selectivity towards tumor tissue. To overcome these limits, bioconjugates of gemcitabine were studied using poly(ethylene glycol) as polymeric carrier. Two types of conjugates were prepared, non-targeted and folic acid targeted conjugates. The formers were obtained starting from mPEG-OH of 5 and 20 kDa with linear or branched structure. The folic acid targeted conjugates, differing for the drug loading, were prepared exploiting a heterobifunctional PEG that allowed a consecutive coupling of the targeting agent and the drug. Folic acid was chosen as targeting agent because its receptor is often over-expressed in many tumors. To increase the polymer drug payload, the bicarboxylic amino acid, aminoadipic acid, was used. All conjugates were able to release the drug in a pH-dependent manner with no role of enzymes. The pharmacokinetic profiles are strictly related to the polymer molecular weight and the folic acid targeting increased 2-3 times the affinity towards the cells over-expressing folic acid receptors. These results are promising and encourage in vivo studies on these conjugates that act as polymeric prodrugs.