Polyomaviruses are small non-enveloped DNA viruses infecting birds and mammals, including human. Their capsid consists of the major capsid protein, VP1, and two minor capsid proteins, VP2 and VP3. The VP2 and VP3 proteins are supposed to have an important function in the transport of viral genome into the cell nucleus, which is a key step to facilitate viral replication. VP2 and VP3 proteins of mouse polyomavirus and SV40 have an ability to bind and disrupt cellular membranes. This feature is believed to be involved in the transport of viral genome into the nucleus. Plasmids carrying genes of the minor capsid proteins of Merkel cell polyomavirus were prepared in order to produce and visualize these proteins in mammalian cells. These proteins are known to have very unusual sequences compared to other human polyomaviruses or related mouse polyomavirus. When produced alone, the minor capsid proteins of Merkel cell polyomavirus did not significantly interact with cellular membranes, unlike the minor proteins of the mouse polyomavirus. The second goal of this work was to prepare mouse polyomavirus mutants with deletion in hydrophobic domains of VP2 and VP3 proteins. These domains are likely responsible for the mentioned membrane interactions. Prepared mutants were non-infectious. The loss of infectivity was not...

Cette thèse porte sur les suites de la paix d’Apamée sur le plan des relations politiques entre les États d’Anatolie et sur l’évolution de la place tenue par cette péninsule dans l’ordre géopolitique méditerranéen. Le traité d’Apamée, conclu en 188 avant notre ère entre la puissance romaine et le royaume séleucide, fut un acte diplomatique majeur pour l’Asie Mineure et l’ensemble de la région anatolienne, libérés de la domination des Séleucides. Jusqu’ici l’historiographie traditionnelle a abordé ce sujet selon deux perspectives, à savoir l’apparition de l’impérialisme romain en Orient et la vie politique et administrative des cités égéennes. À l’inverse, cette étude se concentre sur les principales puissances politiques de la région anatolienne : les royaumes. Dans le cadre de cet espace fragmenté et diversifié, des modifications de l’équilibre géopolitique régional peuvent être mises en relation avec le bouleversement de l’ordre méditerranéen, par le croisement de sources grecques, latines et orientales, ainsi qu’en faisant usage de procédés développés par le courant de la World History. L’évolution ultérieure de la situation mise en place à Apamée est suivie jusqu’à la disparition d’une Anatolie dirigée par des souverains non incorporés dans l’horizon impérial des grandes puissances étrangères, situation à laquelle les ultimes défaites de Mithridate VI du Pont et de Tigrane d’Arménie face à Rome mirent un terme définitif. / This thesis examines the effects of the peace of Apamea with regard to the political relations between the Anatolian states and analyses the importance that this region played in Mediterranean politics following this accord. The treaty of Apamea, concluded in 188 BC between Rome and the Seleucid kingdom, became a diplomatic milestone for Asia Minor and the entirety of Anatolia, then freed from Seleucid domination. The study of this subject has a long tradition in modern historiography, which consists of works focused on either the appearance of Roman imperialism in the East, or the political and administrative lives of the Greek cities. This study is specifically devoted to the central political powers of the Anatolian peninsula; that is to say, the independent kingdoms of Anatolia. The changes seen on the geopolitical balance of this fragmented region can be linked to the profound modifications on the scale of the whole Mediterranean. The sources considered include Greek, Latin and oriental documents and artefacts, as well as some “World History” theoretical approaches. The further evolution of the Apamean order can then be followed up until the disappearance of any powerful local power outside the foreign nations incorporated into imperial rule. The simultaneous defeats of Mithridates VI of Pontus and Tigranes of Armenia against Rome mark the end of this situation where independent kingdoms in this region pursued their own autonomous foreign policies.

The development of palliative care in Indonesia has been slow due to the absence of palliative care guide lines and standards. This results in the limited provision of palliative care where it can only be found available in 14 hospitals in the whole country with a population over 260 million, and the palliative care is basically directed to adult patients. In the paediatric medicine field, the palliative care services in Indonesia is still in its infancy and currently palliative care is served by only one non-profit organization in Jakarta. With around 1,5 million people in Jakarta associated with living in poverty, this organization is focusing on providing free palliative care to children from marginalized communities. The questions that are raised out of these circumstances are how paediatric palliative care is practiced in Jakarta and what the rewarding and challenging parts of the job are. The aim of the study is to describe nurses' perspectives and experiences in giving home-based palliative care to children living with cancer and HIV from marginalized communities in Jakarta. A qualitative study design with content analysis was considered to be the method that fitted the goal of the study best. Semi structured interview was used as data collection method and there were seven nurses who participated in the interviews. The result is described by two main categories; the first category contains different topics that functioned as encouragements to the nurses, and the second category consists of various subjects that contribute to challenges that nurses encounter in their work. Lack of palliative education that lead to certain attitudes in the referral process, misperceptions about pain management and nurses’ stress management are discussed as some challenges encountered in the implementation of palliative care.

La Partition de l’Inde (1947) et la Guerre de libération du Bangladesh (1971) sont deux moments de transition qui exposent la violence de constructions nationales post-coloniales. Les actes perpétrés sur une base ethno-religieuse ont donné lieu à des récits privés pourtant occultés au profit de récits nationaux hégémoniques auto-légitimants. Ces récits attestent tout particulièrement de l’instrumentalisation de figures et de corps de femmes comme lieu de marquage de conflits communautaires. Face au silence imposé par les divers appareils d’État patriarcaux, trois générations de romancières ont cherché à renverser les récits hégémoniques en Inde, au Pakistan et au Bangladesh, par le biais d’une fiction romanesque caractérisée par son incoercibilité et son engagement féministe. Leur écriture de fiction répond à la violence de la fracture de l’Histoire par une poétique de la fragmentation, dont le tout dresse un portrait obscène, monstrueux et carnavalesque de la formation d’États-nations contemporains. Cette écriture romanesque, qu’elle soit sous-continentale ou diasporique, résiste à toute forme de frontières (idéologiques, littéraires, commerciales, etc.), et se consolide par sa prise de position à la fois complexe et engagée. La poétique de fragmentation est amenée par des phénomènes linguistiques, littéraires, sociologiques et politiques. Ce corpus se compose de romans couvrant l’ensemble de la deuxième moitié du XXe siècle, publiés (chronologiquement) par Jyotirmoyee Devi, Anis Kidwai, Mumtaz Shah Nawaz, Attia Hosain, Amrita Pritam, Sophia Mustafa, Bapsi Sidhwa, Anita Rau Badami , Shauna Singh Baldwin Meena Arora Nayak, Sorayya Khan, Kamila Shamsie et Tahmima Anam. / The Partition of India (1947) and the Bangladesh Liberation War (1971) are two transitory moments which reveal the violence of post-colonial nation-building. The acts performed upon an ethno-religious basis have given rise to many private stories, themselves stifled by self-legitimating national master narratives. These stories particularly highlight the instrumentalisation of the idea and the bodies of women in carrying out communal conflict. Three generations of women novelists have sought to break the silence imposed by patriarchal State apparatuses and religious radicalism. They turn to the impetuousness of the literary genre of the novel in order to thwart Indian, Pakistani and Bangladeshi master narratives. As such they write back to the violent fracture of History, through a poetics of the fragment, and together draw an obscene, monstrous and carnival-like portrait of contemporary Nation-States. Such novels, whether sub-continental or diasporic, resist all forms of borders (whether ideological, literary, commercial, etc.), driven instead by their commitment to contradiction. The fragmentation which defines them is all at once linguistic, literary, sociological and political. Our study comprises novels written (chronologically) by Jyotirmoyee Devi, Anis Kidwai, Mumtaz Shah Nawaz, Attia Hosain, Amrita Pritam, Sophia Mustafa, Bapsi Sidhwa, Anita Rau Badami , Shauna Singh Baldwin Meena Arora Nayak, Sorayya Khan, Kamila Shamsie and Tahmima Anam.

Nos dias atuais, a preocupação com o meio ambiente vem ocupando espaço considerável nos principais centros de debates. A procura por solventes provenientes de fontes renováveis que possam substituir solventes de origem fóssil em processos industriais se faz necessária. Tradicionalmente o hexano, derivado do petróleo, é utilizado como extratante industrial de óleos de matrizes oleaginosas, no entanto, este solvente apresenta desvantagens em termos de segurança operacional devido à alta toxicidade e inflamabilidade. Neste contexto, a presente dissertação de mestrado objetivou avaliar a viabilidade técnica da substituição do hexano por solventes alcoólicos, etanol e isopropanol na extração do óleo da torta de prensagem de sementes de girassol. A influência das variáveis tipo e grau de hidratação do solvente alcoólico e temperatura foi avaliada sobre a composição em ácidos graxos, a estabilidade oxidativa do óleo extraído e o teor de ácidos clorogênicos, tocoferóis e fosfolipídeos. A matéria prima foi submetida ao processo de extração sólido-líquido em um simples estágio, utilizando os solventes em grau absoluto e hidratado, nas temperaturas de 60 a 90 °C, sendo objetivo de estudo o rendimento do óleo, o teor de proteína em base seca, índice de retenção, teor de água na fase extrato e teor de ácidos clorogênicos. Extrações sequenciais empregando três estágios na temperatura de 90 °C também foram realizadas para avaliar o teor de óleo residual, extração de ácidos clorogênicos, avaliação da estabilidade oxidativa e determinação dos teores de tocoferóis e fosfolipídeos. Em linhas gerais, pode-se inferir que a hidratação do solvente afetou de forma negativa o rendimento da extração e observou-se também que com o aumento da temperatura, aumenta-se a quantidade de material lipídico extraído. O teor de água no solvente favoreceu a extração dos ácidos clorogênicos, sendo que a temperatura não exerceu influência sobre estes resultados. Quando avaliada a extração de tocoferóis, pode-se notar que os solventes isopropanol (absoluto e hidratado) e etanol absoluto possibilitaram maior extração de α tocoferol quando comparados ao etanol azeotrópico. No entanto, os teores de tocoferóis nos óleos extraídos com álcoois foram inferiores aos detectados nos óleos obtidos com hexano. Na avaliação da estabilidade oxidativa pode-se observar que os óleos extraídos com etanol absoluto e azeotrópico apresentaram estatisticamente o mesmo tempo de indução, fato este que pode estar relacionado aos altos teores de fósforo detectados nos óleos obtidos com estes solventes etanólicos, sugerindo assim que estes solventes são capazes de extrair compostos minoritários que atribuem maior estabilidade oxidativa ao óleo. / Nowadays, the concern regarding the environment has taken a considerable amount of space at the main debate centers. The search for solvents which come from renewable sources that are capable of replacing solvents that come from fossils in industrial processes is paramount. Traditionally the hexane derived from oil is used as an industrial solvent for oleaginous sources. However this solvent presents some disadvantages in terms of operational safety due to the high toxicity and inflammability. In this context, this master´s dissertation has aimed to evaluate the technical viability of the replacement of hexane for alcoholic solvents, ethanol and isopropanol in oil extraction from the meal obtained in the pressing stage of sunflower seeds. The influence of the type and level of hydration of the alcoholic solvents and temperature has been evaluated over the composition in fatty acids, the oxidative stability of the extracted oil, the level of chlorogenics acids, of tocopherols and phospholipids. The meal was submitted to the solid-liquid extraction process in one single stage, using the solvents in absolute and hydrated grade from 60 up to 90 °C, hence the purpose of this study the yield of the oil, the protein level in dry basis, mass of adhered solution (retention index), water level in the extract phase and the chlorogenic acids content. Consecutive extractions applying three stages at 90 ºC have also been performed to evaluate the residual oil content, chlorogenic acids yield, evaluation of oxidative stability and the contents of tocopherols and phospholipids. In summary, it can be concluded that the solvent hydration has affected in a negative fashion the performance of the extraction and it was also noticed that, with the rising in temperature, the amount of lipid extract was increased. The level of water in the solvent has favored the extraction of chlorogenic acids since the temperature has not affected the results. Once the tocopherol extractions are analyzed, it is possible to verify that the isopropanol solvents (absolute and hydrated) and absolute ethanol have enabled a larger extraction of α tocopherol when compared to azeotropic ethanol. However, the levels of tocopherol extracted from alcohols were less than the ones obtained from hexane. In the oxidative stability evaluation it was possible to observe that the oils extracted from absolute and azeotropic ethanol have presented statistically the same induction time, a fact which can be related to high levels of phosphorus detected in the oils obtained from ethanol solvents which suggest that such solvents are capable of extracting minor compounds that attribute more oxidative stability to the oil.

Pretende-se contribuir à análise do conceito de narcisismo no pensamento freudiano a partir de três estudos: (1) Um exame das primeiras elaborações sobre o narcisismo, dividido em dois tempos: (i) a origem do termo junto às primeiras descrições e teorias sobre o narcisismo, (ii) sua entrada na teoria freudiana. A ideia central é, por meio de uma visão diacrônica, acompanhar a apropriação e evidenciar as modificações que Freud incide nesse conceito ao adotá-lo em sua metapsicologia. Para isso, então, iremos em um primeiro momento estudar como os primeiros teóricos do narcisismo Alfred Binet, Havelock Ellis, Paul Näcke e Richard von Krafft-Ebing concebiam e conceberam essa noção; para depois pensar a apropriação freudiana em três fontes: na correspondência trocada com Jung, no registro das Atas da Sociedade Psicanalítica de Viena e nos textos freudianos de 1910 a 1913. (2) Um estudo do texto de Freud Introdução ao narcisismo de 1914 texto central para o narcisismo , levando em consideração três aspectos: (i) a lógica interna do texto, (ii) as modificações que a introdução do narcisismo traz à teoria freudiana e (iii) alguns desdobramentos desse conceito no interior do pensamento freudiano. (3) Uma análise da noção de narcisismo das pequenas diferenças desenvolvendo um dos vários desdobramentos que o conceito de narcisismo tem a partir de 1914; trata-se de uma análise sincrônica que visa cotejar e relacionar três momentos dessa noção: tal como ela surge pela primeira vez em O tabu da virgindade de 1918, como ela é retomada em Psicologia das massas e análise do Eu de 1921 e sua versão final em O mal-estar na cultura de 1930. Em suma, o primeiro estudo visa pensar a origem e a entrada do narcisismo no pensamento freudiano; o segundo, o narcisismo na metapsicologia; e o terceiro, o narcisismo enquanto fenômeno social / We aim to contribute to the analysis of the concept of narcissism in the Freudian thought from three studies: (1) An examination of the first elaborations on narcissism, divided into two stages: (i) the origin of the term within the first descriptions and theories of narcissism, (ii) its entry into the Freudian theory. The central idea is, through a diachronic view, to track the appropriation and highlight the changes that Freud makes into this concept to adopt it in his metapsychology. For this, we will at first study how the first theorists of narcissism - Alfred Binet, Havelock Ellis, Paul Näcke and Richard von Krafft-Ebing - conceived this notion, and then think about the Freudian appropriation on three sources: in the correspondence with Jung, in the record of the Minutes of the Psychoanalytic Society of Vienna and in the Freudian texts from 1910 to 1913. (2) A study of the Freudian text On Narcissism: an introduction of 1914 - the central text for narcissism - taking into account three aspects: (i) the internal logic of the text, (ii) the changes that the introduction of narcissism brings to the Freudian theory, (iii) some consequences of this concept inside the Freudian thought. (3) An analysis of the concept of narcissism of minor differences - unfolding one of the several developments that the narcissism concept has had since 1914; it is a synchronic analysis that aims to collate and relate three moments of this notion: such as it first appears in The Taboo of Virginity of 1918, the way it is retaken in Group Psychology and the Analysis of the Ego of 1921, and its final version in Civilization and Its Discontents of 1930. In short, the first study aims to consider the origin and the entry of narcissism in the Freudian thought; the second is related to the narcissism in metapsychology; and the third, narcissism as a social phenomenon

La Pisidie, région montagneuse du sud-ouest de l’Asie Mineure, est un véritable conservatoire toponymique de la culture et des langues anatoliennes. Notre thèse porte sur la toponymie et l’ethnonymie de la Pisidie et sur la persistance des langues anatoliennes dans la toponymie de la région. La toponymie et l’ethnonymie nous révèlent l’emprise sur le territoire de chaque peuplement, qu’il s’agisse du peuplement anatolien ou des peuplements exogènes (principalement grecs et romains). En effet, par le choix de la langue utilisée pour créer le nom du lieu ou du peuple, nous en apprenons davantage sur la région. Après avoir réalisé un catalogue des toponymes et des ethnonymes de la Pisidie classés par types et discuté leur origine à l’aide d’arguments linguistiques pour chacun d’entre eux, nous étudions la présence grecque et les colonies romaines en envisageant les dominations successives du point de vue de la toponymie. Plusieurs thèmes sont abordés : la question du contrôle de la région à l’époque hellénistique, les fondations séleucides, ainsi que les colonies romaines fondées par Auguste. Puis, nous nous concentrons sur l’identité des Pisidiens, en étudiant la question de leur origine et des topoi qui leurs sont associés. Les continuités et les ruptures territoriales de la Pisidie sont abordées avant un panorama toponymique présentant un classement linguistique et un classement sémantique des toponymes en fonction du référentiel sémantique (eau, relief, végétation, etc.). L’essentiel des toponymes est descriptif et renvoie à des éléments du paysage. / Pisidia, a mountainous region in southwestern Asia Minor, is a real toponymic conservatory of Anatolian culture and languages. Our thesis deals with the toponymy and ethnonymy of Pisidia and the persistence of Anatolian languages in the toponymy of the region. Toponymy and ethnonymy reveal the territorial control of each settlement, whether it be Anatolian population or exogenous settlements (mainly Greek and Roman). Indeed, by choosing the language used to create the name of the place or the people, we learn more about the region. After having produced a catalog of toponyms and ethnonyms of the Pisidia classified by types and after having discussed their origin using linguistic arguments for each one, we study the Greek presence and the Roman colonies by considering the successive domination in regard to toponymy. Several themes were discussed : the question of the control of the region during the Hellenistic period, the Seleucid foundations, as well as the Roman colonies founded by Augustus. Then we focus on the identity of the Pisidians, studying the question of their origin and the topoi associated with them. The continuities and territorial cleavage of Pisidia are discussed before a toponymic panorama showing a linguistic classification and a semantic classification of toponyms based on the semantic repository (water, relief, vegetation, etc.). Most of the place names are descriptive and refer to elements of the landscape.

Submitted by admin tede (tede@pucgoias.edu.br) on 2016-09-12T18:27:45Z No. of bitstreams: 1 MARCOS VIEIRA DA SILVA.pdf: 792830 bytes, checksum: 41f6349bb258db4b598c422d46004419 (MD5) / Made available in DSpace on 2016-09-12T18:27:45Z (GMT). No. of bitstreams: 1 MARCOS VIEIRA DA SILVA.pdf: 792830 bytes, checksum: 41f6349bb258db4b598c422d46004419 (MD5) Previous issue date: 2016-03-29 / This paper aims to make an approximation of some concepts of the Philosophy of Difference as proposed by Gilles Deleuze and Felix Guattari to Kafka´s so called Minor Literature, in specific The Metamorphosis and The Trial. For these philosophers, although Literature and Philosophy have different objects, they have bonds and come close to each other when they give their testimony of life. It is life that runs through literature; several types of devir overflow in literary writing: devir-man, devir-woman, devir-child, devir-animal, devir-molecule, imperceptible devir, flows of life and death shaping rizomes, agitating Franz Kafka´s world map. The character Gregor Samsa in Metamorphosis is a man, but a transformed man, turned into an insect, a deviranimal, a devir-molecule, a flow of desire, blocks of sensation. Kafka´s world is truly agitated, the political machine, the war machine are all connected, disconnected and re-connected, shuffling the codes in The Trial and in Metamorphosis and as they were shuffled, they took language to the limit, forcing thought to think and language to stutter, because language and thought fold themselves inside and outside through the forces of sign. In this movement between the inside and the outside, we are led to weave our third margin. Pointing the possible connections between Deleuze´s Philosophy of Difference and Literature, searching in the reflections, experimentation with some concepts such as sign, rizome, desire, agency, flows, machines and the concept of Minor Literature as a field of aesthetical experimentation, is the intention of this work. / O trabalho tem como objetivo aproximar alguns conceitos da filosofia da diferença de Gilles Deleuze e Felix Guattari com a literatura dita menor de Franz Kafka, mais especificamente nas obras A Metamorfose e O Processo. Para esses filósofos, embora a literatura e a filosofia tenham objetos diferentes, elas fazem elos, se aproximam quando testemunham a vida. É a vida que corre na literatura, devires diversos transbordam na escrita literária. Devir-homem, devir-mulher, devir-criança, devir-animal, devir-molecular, devirimperceptível, fluxos de vida e de morte fazem rizomas, agitando o mapamundo de Franz Kafka. O personagem Gregor Samsa na Metamorfose é um homem, mas um homem transformado, modificado em um inseto, um deviranimal, um devir-molecular, um fluxo de desejo, blocos de sensação. O mundo de Kafka é uma verdadeira agitação, máquina política, máquina de guerra conectam, desconectam e reconectam embaralhando os códigos no Processo e na Metamorfose e ao embaralhar leva a linguagem ao seu limite, forçando o pensamento a pensar e a língua a gaguejar, porque a linguagem e o pensamento dobram dentro e fora pela força do signo. Nesse movimento entre dentro e fora somos levados a tecer a nossa terceira margem. Apontar as possíveis conexões entre filosofia da diferença de Deleuze e da literatura, procurando a partir das reflexões, experimentar alguns conceitos como signo, rizoma, desejo, agenciamento, fluxos, máquinas, e do conceito de literatura menor enquanto campo de experimentação estética, é o que se pretende na proposta deste trabalho.

Submitted by admin tede (tede@pucgoias.edu.br) on 2017-04-25T12:32:21Z No. of bitstreams: 1 Larissa Queiroz Azevedo de Aquino.pdf: 919571 bytes, checksum: e822d1ea73d19d8479ab22889fd69c9d (MD5) / Made available in DSpace on 2017-04-25T12:32:21Z (GMT). No. of bitstreams: 1 Larissa Queiroz Azevedo de Aquino.pdf: 919571 bytes, checksum: e822d1ea73d19d8479ab22889fd69c9d (MD5) Previous issue date: 2017-03-13 / The present study had as objective to evaluate the antecedent and consequent events that maintained the problem behaviors of an adolescent who served sentence in institution for minor offender; Also aimed at treating these behaviors. The participant was male, single, aged 17 years. In order to evaluate, it was used strategies of the process of functional evaluation by indirect observation, direct observation of its behaviors at various moments in the institution and functional (experimental) analysis. The functional analysis involved the manipulation of environmental events in four main conditions: attention, demand, alone and control. The attention condition was subdivided into: (1) attention-warning, (2) attention-reprobation and (3) attention-concern. The results showed that there was a greater register of problem behaviors in the attention and demand conditions, than in the conditions alone and control, evidencing, therefore, that these behaviors were maintained by sources of positive and negative reinforcement. In order to deal with the participant's problem behaviors, the differential reinforcement of alternative behaviors was employed, combined with their extinction, thus making it possible to reduce them and increase the desired behaviors. For the control of procedures, the ABAB-type replication-replication design was used, followed by follow-up. It was observed that problem behaviors are susceptible to extinction, as well as social attention can be considered reinforcing to obtain desirable behaviors. The objectives of this study were achieved, proving, as in other studies in the literature, that through the application of behavioral analysis strategies, it is possible to increase the frequency of desired behaviors in adolescents who were serving their sentence in an institution for minor offenders. / O presente estudo teve como objetivo avaliar os eventos antecedentes e consequentes que mantinham os comportamentos-problema de um adolescente que cumpria pena em instituição para menor infrator; objetivou também tratar esses comportamentos. O participante era do sexo masculino, solteiro, com idade de 17 anos. Para avaliar, utilizou-se de estratégias do processo de avaliação funcional por observação indireta, observação direta de seus comportamentos em vários momentos na instituição e análise funcional (experimental). A análise funcional envolveu a manipulação de eventos ambientais em quatro condições principais: atenção, demanda, sozinho e controle. A condição atenção foi subdividida em: (1) atenção-advertência, (2) atenção-reprovação e (3) atenção-preocupação. Os resultados mostraram que houve maior registro de comportamentos-problema nas condições de atenção e demanda, do que nas condições sozinho e controle, evidenciando, portanto, que estes comportamentos foram mantidos por fontes de reforçamento positivo e negativo. Para tratar os comportamentos-problema do participante foi empregado o reforçamento diferencial de comportamentos alternativos combinado com extinção, possibilitando assim reduzí-los e aumentar os comportamentos desejados. Para o controle dos procedimentos foi usado o delineamento de reversão-replicação do tipo ABAB, seguido de follow-up. Foi observado que comportamentos-problema são suscetíveis à extinção, bem como a atenção social pode ser considerada reforçadora para obtenção de comportamentos desejáveis. Os objetivos desse estudo foram alcançados, comprovando, assim como em outros estudos existentes na literatura, que através da aplicação das estratégias da análise do comportamento, torna-se possível aumentar a frequência de comportamentos desejados em adolescente que cumpria pena em instituição para menor infrator.

O presente estudo teve como objetivos avaliar os efeitos ecotoxicológicos das ações individual e combinada dos fármacos cloridrato de propranolol e losartana potássica, por meio do ensaio de inibição do crescimento da macrófita aquática Lemna minor e comparar esses efeitos com os preditos por meio dos modelos de adição de concentração e ação independente. Buscou-se também calcular critérios de qualidade da água para a proteção da vida aquática para esses dois fármacos. Os testes de sensibilidade foram realizados empregando-se o cloreto de sódio como substância de referência. Os testes ecotoxicológicos foram conduzidos de acordo com Protocolo da OECD, com a modificação do uso de fotoperíodo ao invés de luz contínua para simular condições ambientais mais realísticas. As bases de dados Ecotox Database e da National Centers for Coastal Ocean Science foram consultadas, respectivamente, para a obtenção de dados ecotoxicológicos para a derivação dos critérios de qualidade da água e para a obtenção de dados previstos por meio de relações quantitativas estrutura-atividade (RQEA). Com relação aos testes de sensibilidade, todos os resultados estiveram dentro da faixa de aceitabilidade ao nível de confiança de 95%, com um valor médio de concentração efetiva mediana (CE50) de 4042,6 mg.L-1. Os testes com o fármaco cloridrato de propranolol para os parâmetros número de frondes, área foliar total e peso fresco resultaram nos valores médios de CE50 respectivos de 101,4 mg.L-1; 76,2 mg.L-1 e 84,0 mg.L-1, enquanto que nos testes com a losartana potássica esses valores foram, respectivamente, de 63,9 mg.L-1; 61,3 mg.L-1 e de 76,9 mg.L-1. Os valores de CENO e de CEO obtidos nos testes com o cloridrato de propranolol foram de 1,56 mg.L-1 e 3,1 mg.L-1, respectivamente, enquanto que nos testes com a losartana potássica, esses valores foram de 0,78 mg.L-1 e de 1,56 mg.L-1. O teste de ação combinada com os fármacos mostrou que ambos os modelos preditivos superestimaram, em todos os níveis de concentração testados, os efeitos de toxicidade da mistura nos testes com a L. minor. Portanto, observaram-se interações antagonísticas na ação combinada desses dois fármacos em relação aos efeitos preditos pelos modelos de referência. Com relação aos critérios de qualidade da água, calcularam-se os valores de 0,9 e 0,18 µg.L-1 de cloridrato de propranolol para a proteção das espécies pelágicas de água doce e salina, respectivamente, enquanto que para a losartana potássica, os valores preliminares calculados para a proteção das espécies de água doce e marinhas foram, respectivamente, de 0,055 e de 0,0055 µg.L-1. Os resultados obtidos permitiram observar que a losartana potássica mostrou-se mais tóxica para L. minor do que o cloridrato de propranolol. Além disso, a macrófita mostrou-se mais sensível aos efeitos de toxicidade da losartana potássica do que outras espécies relatadas na literatura. O teste de mistura mostrou que a capacidade dos dois modelos avaliados em predizer a toxicidade de misturas é limitada. As concentrações do cloridrato de propranolol em ambientes aquáticos não ultrapassam os critérios de qualidade da água. Testes crônicos adicionais com a losartana são necessários para a derivação de critérios definitivos. / This study aimed to evaluate the single and joint ecotoxicological effects of the drugs propranolol hydrochloride and losartan potassium, using the Lemna minor growth inhibition test and to compare the observed effects with those predicted by the models of concentration addition and independent action. In addition, water quality criteria were derivated for the protection of aquatic life against the possible adverse effects caused by these antihypertensive drugs. The sensitivity tests were carried out employing sodium chloride as a reference substance. Ecotoxicological tests were carried out according to OECD protocol, with the modification of using photoperiod instead of continuous lighting, in order to provide conditions closer to the environmental ones. The Ecotox Database and the database of the National Centers for Coastal Ocean Science were consulted for derivation of the water quality criteria and for the data predicted by quantitative structure-activity relationships (QSARs), respectively. With regard to the sensitivity tests, all results were within the range of acceptability at a 95% confidence level, with a mean value of median effective concentration (EC50) of 4042.6 mg.L-1. The tests with propranolol hydrochloride for the parameters frond number, total frond area and fresh weight resulted in mean EC50 values of 101.4 mg.L-1; 76.2 mg.L-1 and 84.0 mg.L-1, respectively, whereas in the tests with losartan potassium, those EC50 values were 63.9 mg.L-1, 61.3 mg.L-1 and 76.9 mg.L-1, respectively. The NOEC and LOEC values obtained in the tests with propranolol hydrochloride were 1.56 mg.L-1 and 3.1 mg.L-1, respectively, whereas in the tests with losartan potassium, these values were 0.78 mg.L-1 and 1.56 mg.L-1, respectively. Both the reference predictive models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated in the L. minor test. Therefore, the mixture of propranolol hydrochloride and losartan potassium showed an antagonistic interaction in the L. minor test in comparison to the predicted effects. Regarding to the water quality criteria, the values of 0.9 and 0.18 µg.L-1 of propranolol hydrochloride were calculated for the protection of pelagic organisms living in freshwater and marine ecosystems, respectively, whereas for losartan potassium, the calculated preliminary criteria for protection of pelagic organisms living in freshwater and saltwater ecosystems were 0.055 and 0.0055 µg.L-1, respectively. The results showed that losartan potassium proved to be more toxic to L. minor than propranolol hydrochloride. Furthermore, this macrophyte seemed to be more sensitive to losartan toxicity than other organisms reported in the literature. The mixture test showed that the capability of the two reference models in accurately predicting the mixture toxicity is limited. The concentrations reported of propranolol hydrochloride in aquatic environment are not usually higher than the water quality criteria values. More data on chronic test to losartan are necessary in order to derive definitive criteria.