Submitted by Liliane Úbeda Morandi Rotoli null (lilianemorandi@yahoo.com.br) on 2016-07-25T12:32:17Z No. of bitstreams: 1 LilianeUbedaMorandiRotoli_PGAD_TUPA_Abril2016.pdf: 4209302 bytes, checksum: cce94f81cce55574df2e78b200a15c4c (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-07-28T11:57:46Z (GMT) No. of bitstreams: 1 rotoli_lum_me_tupa.pdf: 4209302 bytes, checksum: cce94f81cce55574df2e78b200a15c4c (MD5) / Made available in DSpace on 2016-07-28T11:57:46Z (GMT). No. of bitstreams: 1 rotoli_lum_me_tupa.pdf: 4209302 bytes, checksum: cce94f81cce55574df2e78b200a15c4c (MD5) Previous issue date: 2016-04-04 / A agricultura familiar depara-se com diversas barreiras no sistema agropecuário brasileiro. Pode-se citar a falta de estrutura de escoamento da produção, carência de recursos, distância do mercado consumidor e a distribuição do produto no que se refere ao acesso ao mercado e custos das transações. Uma estratégia de diferenciação para os agricultores familiares e que contribui para a competitividade é a produção de produtos orgânicos. Em razão da fragilidade dos agricultores familiares na distribuição dos produtos o agricultor deve eliminar intermediários, e sendo assim, o canal direto de comercialização se torna um mecanismo eficiente para o agricultor. O objeto de análise do presente estudo utilizou o canal direto Community Supported Agriculture (CSA), que é um mecanismo de comercialização de produtos da agricultura, que tem como proposta sustentar a agricultura, especificamente relacionada ao manejo orgânico, por meio de uma proximidade maior entre ambos agentes, agricultor e consumidor, sendo que este último se compromete a realizar pagamentos antecipados para que o agricultor possa produzir seus produtos e planejar a sua produção. Esta pesquisa foi motivada pela análise da relação de comercialização entre os agricultores e consumidores, e utilizou a teoria da Economia dos Custos de Transação (ECT) para dar embasamento teórico à pesquisa. Portanto, o objetivo principal deste estudo foi analisar a estrutura de governança utilizada nas CSAs do Estado de São Paulo e o alinhamento das características das transações e das características dos agentes agricultores e consumidores envolvidos. A pesquisa teve natureza quali - quantitativa, com aplicação do método survey. Os dados foram coletados entre dezembro de 2015 e janeiro de 2016 com 241 famílias (27,5% da população) e 11 agricultores (91,6% da população) do Estado de São Paulo. Os resultados indicaram que a motivação dos agricultores em participar das CSAs envolvem fatores ambientais, proximidade com o consumidor e ideologias, já para os consumidores, o que os motiva são fatores relacionados ao meio ambiente, produtos de qualidade e procedência, e ajudar um agricultor. A análise do ambiente institucional mostrou que a legislação de produção orgânica brasileira é a única regra formal sobre a atividade. Os agricultores e consumidores das CSAs analisadas apresentaram bom alinhamento quanto às características das transações e dos agentes, de modo geral. Os agricultores e consumidores apresentaram desalinhamento quanto à incerteza, mostrando que há necessidade de adaptações no acordo (formal/informal) entre os agentes. Existe racionalidade limitada entre os agentes, uma vez que não há troca de informação em relação a alguns aspectos da transação como por exemplo qualidade e quantidade dos produtos consumidos, previsão de volume produzido, e isto prejudica a previsão de transações futuras. Por fim, a estrutura de governança identificada na relação de comercialização entre agricultores e consumidores é a híbrida e é adequada para a eficiência da coordenação e diminuição dos custos de transação. No entanto, sugere-se que sejam incorporados alguns elementos no acordo para reduzir o nível de incerteza do agricultor, e ainda que tal acordo seja formalizado entre ambas as partes. / Family farming faces several barriers in the Brazilian Agricultural System. Such barriers include the lack of flow of production structure, lack of resources away from the consumer market, distance from the consumer market and the distribution of the product in relation to market access and transaction costs. A differentiation strategy for family farmers that contributes to competitiveness, is the production of organic products. Due to the fragility of family farmers in the distribution of farm products, the elimination of the middleman results in a direct marketing channel, which creates an efficient mechanism for the farmer. The analysis of a current study used the direct channel Community Supported Agriculture (CSA), which is a marketing mechanism for agriculture products used directly between farmer and consumer. The CSA have also proposed a form of sustainable agriculture, specifically related to organic farm management. By having the agents, farmers and consumers, work more closely together, prepayments may be made to the farmer in order to produce products and plan production. This research was conducted in order to analyze the marketing relationship between farmers and consumers, and used the theory of Tansaction-Costs Economics (ECT) to give theoretical basis for research. Therefore, the main objective of this study was to analyze the governance’s structure used in the CSAs of the São Paulo State and the alignment of the transaction characteristics and the characteristics of farmers’ agents and consumers involved. The research was qualitative and quantitative in nature and was applied using the Survey Method. The data was collected between December of 2015 and January of 2016 with 241 families (27.5% of the population) and 11 farmers (91.6% of the population) of São Paulo. The results indicated that the motivation of farmers to participate in CSAs involve environmental factors, as well as proximity to the consumer and ideologies. In contrast, consumers were motivated by factors that related to the environment, product quality and origin, and in the interest of helping the farmer. The analysis of the institutional environment showed that Brazilian organic production legislation is the only formal rule relevant to the activity. The farmers and consumers of CSAs that were analyzed showed good alignment on the characteristics of the transactions between agents. Farmers and consumers showed misalignment as the uncertainty, showing that there is need for adjustments to the agreement (formal / informal) between agents. There is a limited rationality between agents, since there is no exchange of information in relation to some aspects of the transaction such as: quality and quantity of consumed products, prediction of production volumes, and this impairs the prediction of future transactions. Overall, the governance structure identified in the marketing relationship between farmers and consumers is the hybrid and is appropriate for coordination efficiency and decreased transaction costs. However, certain elements, such as the formalization of the arrangements between both parties, should be incorporated within the deal in order to reduce the farmer's level of uncertainty.

Programmed death-1 (PD-1) et ses ligands PD-L1 et PD-L2 appartiennent à la famille B7 : CD28 des molécules de cosignalisation immunitaire. Leur interaction délivre un signal inhibiteur à l’activation lymphocytaire. Ces molécules sont impliquées non seulement dans le contrôle de la tolérance, mais aussi dans un mécanisme d’échappement tumoral et viral au système immunitaire. Les deux ligands de PD-1 : PD-L1 et PD-L2 montrent une expression tissulaire assez large, témoignant de leur rôle étendu aux différents stades de la réponse immunitaire. L’expression de PD-L1 est plus large que celle de PD-L2. PD-L1 est exprimé sur les cellules hématopoïétiques et non hématopoïétiques, PDL2 présente une expression assez restreinte aux CPAs professionnelles. L’expression de PD-L1 et PD-L2 est fortement régulée dans plusieurs cas pathologiques et notamment dans les cancers. La régulation de l’expression de PD-L2 qui fait l’objet de notre étude, représente une cible importante dans le domaine de l’immunothérapie. Notre projet porte sur l’analyse de l’expression, la régulation et la fonction de PD-L2 dans les LT, dans différents contextes physiologiques et pathologiques. Nous avons pu démontrer que PD-L2 qui avait été décrit chez la souris pour son expression restreinte aux CDs et aux macrophages, était de façon surprenante exprimé avec son homologue PD-L1 sur les LT après costimulation CD3+CD28. Nous l’avons confirmé ex vivo par activation par Staphylococcal enterotoxin E. Ce résultat montre que PD-L2 est bien induit sur des LT dans des conditions d’activation physiologique ou pathologique. Nous avons pu démontrer aussi une régulation négative de l’expression transcriptionnelle et protéique de PD-L1 et de PDL2 sous l’effet de la CyclosporineA (CsA). Cet effet est indépendant de l’action de l’IL-2. Nos données d’analyses bioinformatiques nous ont permis d’identifier les sites putatifs de fixation de facteurs de transcription au niveau du promoteur du gène pd-l2, qui peuvent être régulés par la CsA. L’analyse de la fonction de PDL2 sur les LT nous a permis de démontrer que la stimulation de PDL2 par des anticorps monoclonaux fabriqués dans le laboratoire inhibait l’activation T. Nos résultats démontrent pour la première fois une fonction de PDL2 et une signalisation « reverse siglaling » dans les LT potentiels. La caractérisation fonctionnelle et l’étude des voies de signalisation de PD-L2 que nous avons déjà étudié dans notre projet, représentent une piste importante à explorer. Cela permettrait de proposer de nouvelles stratégies permettant de lutter contre les mécanismes d’échappement tumoral. / PD-1 (programmed death-1) is a new CD28 families member, that deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. (1) (ref octa).PD-1, is inducibly expressed on T cells. The PD-1 ligands PD-L1 (B7-H1) and PD-L2 (B7-DC) exhibit distinct patterns of expression: PD-L1 is expressed more broadly than is PD-L2. PD-L1 is expressed on resting and up regulated on hematopoietic, nonhematopoietic cells and cancer cell. However, PD-L2 is expressed only on professional antigen-presenting cells. In addition, it has been demonstrated that PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cytokines.Suggesting that PD-L2 is regulated differently in the former versus the latter, and this proved to be the case, both in transcription and promotion (2) (ref octa) However, little is known about the regulation of PD-L2 expression and nine is known about the expression of PD-L2 on T cells. In the present study, we observed in the first time, by flow cytometer and real time PCR (RT PCR) that PD-L2 expression is induced on ex vivo on activated CD4+ and CD8+ T cells, on in vitro on activated JURKAT T cell line and this expression is inhibited by the immunosuppressive drogue Cyclosporin A (CsA). In the second time we showed that PD-L2 is up regulated in vivo on Non hodchkin lymphoma, other up regulation of PD-L2 expression is observed on Vb8+ T cells after PBMC treatment with the Staphylococcal enterotoxin E (SEE) super antigen. Finally, we attributed a function to PD-L2 to be a co-inhibitory molecule for CD4+ T cells activation.

This thesis is focused on monitoring attributes of ettringite in long term horizon, especially on his thermodynamic stability. Ettringit was prepared in two ways. Firstly, it is a method of hydration of yeelimite, secondly, ettringit is prepared by addition of aluminium sulphate and calcium hydroxide.

Sexuell exploatering av barn på nätet är ett fenomen som ökat substantiellt i takt med att internetanvändningen ökat i dagens samhälle. Forskning tyder på en ökning med ca 100 fall år 2020 jämfört med år 2019. Sexuell exploatering är i sig inte ett nytt fenomen, men den typen som sker via nätet kan betraktas som en ny form av exploatering som bör studeras närmare. Denna nya form av sexuell exploatering har bidragit till skapandet av en ny typ av förövare, som opererar anonymt och i många avseenden oreglerat. Syftet med det här arbetet är att undersöka hur välutrustade olika sociala aktörer som socialtjänst och fristående organisationer är för att bemöta barn som blivit sexuellt exploaterade på nätet samt identifiera vilka brister som förekommer i dagsläget. I arbetet genomförs sex semistrukturerade intervjuer med yrkesverksamma både inom socialtjänsten och fristående organisationer. Intervjuresultaten delas därefter in i fyra olika identifierade teman: Yrkesverksammas bemötande av utsatta barn, Är yrkesverksamma välutrustade för att bemöta barn som utsatts för sexuell exploatering via nätet?, Barn i riskzon för sexuell exploatering samt Olika typer av sexuell exploatering. Dessa teman analyseras, huvudsakligen utifrån systemteorin, foten-i-dörren metoden samt tidigare forskning inom ämnet, och även Barns-Behov-I-Centrum-arbetssättet (BBIC) då det genomsyrar socialtjänstens arbete med barn. / Sexual exploitation of children online is a phenomenon that has significantly increased in occurrence apace with the amplified use of the internet in today's society. Current research indicates an incline of about 100 more cases in 2020, compared to the year prior. Sexual exploitation in itself is not a new phenomenon, however the technology assisted exploitation can be considered a new form that needs more research. With a new problem follows the creation of a new type of perpetrator that operates anonymously and often unregulated. The purpose of this study is therefore to investigate how well-equipped different social work practitioners are to face this new phenomenon as well as to identify shortcomings that may exist. This study includes six semi-structured interviews with both social workers with a Degree of Bachelor of Science in Social Work and individuals within independent organizations targeting this phenomenon. The interview results were consequently divided into four different identified themes: Professionals' treatment of subjected children, Are professionals well-equipped to face children subjected to sexual exploitation online?, Children in risk zones, and Different types of sexual exploitation. The themes were subsequently analyzed, mainly on the basis of system- and the foot-in-the-door theory, previous research and Childrens-Needs-In-Center perspective (BBIC).

The continuous emergence of drug-resistance pathogens is a global concern. As a result, substantial effort is being expended to develop new therapeutics and mechanisms for controlling microbial growth to avoid entering a "post-antibiotic" era in which commonly used antibiotics are no longer effective in treating infections. In this work, we investigate the efficacy and application of ceragenins as non-peptide mimics of antimicrobial peptides (AMPs). First, this work examines the susceptibility of drug-resistant Gram-negative bacteria. The susceptibility of colistin-resistant clinical isolates of Klebsiella pneumoniae to ceragenins and AMPs suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs. Furthermore, Lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. Next, we investigated the potential for cross resistance between chlorhexidine, colistin, AMPs and ceragenins as repeated exposure of bacteria to chlorhexidine might result in cross resistance with colistin, AMPs or ceragenins. Furthermore, a proteomics study on the chlorhexidine-resistant strains showed that chlorhexidine resistance is associated with upregulation of proteins involved in the assembly of LPS for outer membrane biogenesis and virulence factors in Pseudomonas aeruginosa.Second, this dissertation describes the antifungal activity of ceragenins against an emerging multidrug-resistant fungus, Candida auris. We found that lead ceragenins displayed activities comparable to known antifungal agents against C. auris isolates. We also found that fungal cell morphology was altered in response to ceragenin treatment, that ceragenins exhibited activity against sessile organisms in biofilms, and that gel and cream formulations including CSA-44 and CSA-131 resulted in a significant log reduction against established fungal infections in ex vivo mucosal tissues. Finally, a hydrogel film containing CSA-131 was generated on endotracheal tubes (ETTs). ETTs provide an abiotic surface on which bacteria and fungi form biofilms that cause serious infections. In this study, the eluting ceragenin prevented fungal and bacterial colonization of coated ETTs for extended periods while uncoated tubes were colonized by bacteria and fungi. Coated tubes were well tolerated in intubated pigs. The ability of ceragenins to eradicate established biofilms make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. In ex vivo studies, we initially found that this ceragenin, at concentrations necessary to eradicate established biofilms, also causes loss of cilia function. However, by formulating CSA-131 in poloxamer micelles, cilia damage was eliminated and antimicrobial activity was unaffected. These findings suggest that CSA-131, formulated in micelles, may act as a potential therapeutic for polymicrobial and biofilm-related infections in the lung and trachea.

O modelo convencional de organização da cadeia de produção e distribuição de alimentos é baseado na dependência cada vez maior do capital financeiro e industrial, no uso de agroquímicos, adubos, fertilizantes industriais e de outras técnicas provenientes da Revolução Verde, na livre circulação de mercadorias nos países e na inserção de intermediários na cadeia de distribuição. Esse modelo representa um movimento de mercantilização da agricultura e prejudica a autonomia dos indivíduos sobre a sua reprodução material e social, fazendo com que a sociedade enfrente um incremento de pobreza, insegurança alimentar, êxodo rural, danos à saúde e ao meio ambiente, assim como uma perda do senso de comunidade e de solidariedade. Além da compreensão do conceito e das formas de expressão do movimento de mercantilização, a lente teórica, que tem origem em Karl Polanyi, possibilita capturar o conceito da pluralidade e da coexistência dos princípios de regulação econômica e também do contramovimento como uma forma de resistência e de resgate da autonomia relativa dos indivíduos. É nesse contexto que a Agricultura Sustentada pela Comunidade (CSA) surge como uma possibilidade de contramovimento ao mercado convencional de alimentos ao adicionar uma qualidade ao ato de alimentar-se pela produção agroecológica e ao reconectar produção e consumo mediante o encurtamento da cadeia de distribuição. O problema que norteou a pesquisa desta dissertação foi compreender quais seriam as formas de contramovimento que se configuram na Agricultura Sustentada pela Comunidade diante da generalização do processo de mercantilização. Por isso, o objetivo geral consistiu em compreender e analisar, em uma experiência real de CSA situada na região sudeste do Brasil, os padrões de troca não mercantil em operação e os fatores que favorecem a autonomia relativa e elevam a coesão social de produtores e consumidores que participam da experiência observada. O método empregado foi a observação participante, utilizando as técnicas da etnografia. Em termos gerais, os resultados encontrados na pesquisa sinalizam que os indivíduos não são passivos diante dos efeitos da mercantilização e articulam-se em movimentos que buscam proteção e ganho de autonomia. Os resultados confirmam a hipótese inicial de que nas atividades de CSA coexistem, com a troca de mercado, outros princípios de regulação da economia, especificamente a reciprocidade, que aparece em diversos momentos, desde as motivações para o engajamento dos indivíduos até a forma em que a própria troca é realizada. Isso porque ao privilegiar nas suas trocas o ato em vez do objeto e do interesse privado, há menção a uma relação mais humana que permite o estabelecimento de amizade, solidariedade, tolerância, fidelidade e comprometimento mútuos, mas, principalmente, possibilita a ampliação da autonomia relativa dos indivíduos e o estabelecimento de um senso de comunidade, que se faz em torno do alimento. Na pesquisa, foram identificados três fatores específicos desta eficácia: a forma de produzir o alimento, oposto ao da agricultura tradicional, o encurtamento da cadeia e as atividades em conjunto mobilizadas pelo grupo de agricultores e consumidores. Desta forma, a Agricultura Sustentada pela Comunidade constitui um contramovimento à mercantilização na agricultura e aparece como uma alternativa eficaz na construção da autonomia daqueles que estão entrelaçados nessa rede de alimentos e na ampliação da coesão social. Os resultados e conclusões apresentados ao longo da dissertação ganham relevância na medida em que contribuem com novas informações e possibilidades de atuação na reversão do êxodo rural, na diminuição da pobreza, na redução de gastos públicos em saúde com uma alimentação mais saudável, assim como na promoção de iniciativas de preservação do meio ambiente. / The conventional model of organization of the production and distribution of food chain is based on the increasing dependence on the financial and industrial capital, the use of agrochemicals, fertilizers, industrial fertilizers and other techniques from the Green Revolution, the free circulation of goods in countries and the inclusion of intermediaries in the distribution chain. This model represents a movement of commodification of agriculture and undermines the autonomy of individuals concerning their material and social reproduction, leading society to a status of poverty, food insecurity, rural exodus, damage to health and environment, as well as to a loss of sense of community and solidarity. In addition to understanding the concept and the ways of expression of the commodification movement, the theoretical approach, based on Karl Polanyi, enables to capture the concept of plurality and coexistence of the principles of economic regulation and also the countermovement as a form of resistance and rescue of the individuals’ autonomy. In this context, the Community-Supported Agriculture (CSA) emerges as a possibility of countermovement to the conventional food market to add quality to the act of feeding by the agroecological production and to reconnect production and consumption by shortening the supply chain. The problem that guided the research of this dissertation was to understand what are the forms of countermovement that are present in the Community-Supported Agriculture before the generalization of the commodification process. Therefore, the overall objective was to understand and analyze, in a real experience of CSA located in southeast region of Brazil, the patterns of non-market exchange and the elements that favor the relative autonomy and increase social cohesion among producers and consumers participating in the observed experience. The method used was participant observation, using the techniques of ethnography. In general, the results found in the study show that individuals are not passive before the effects of commodification and they articulate in movements that seek protection and autonomy. The results confirm the initial hypothesis that, in the CSA, activities coexist with the exchange market, such as other principles of regulation of economy, especially reciprocity, which appears at various times, in motivation for engagement and in the way the exchange itself is performed. This happens because, when they prioritize their exchanges act instead of the object and the private interest, they develop a more human relationship that allows the establishment of friendship, solidarity, tolerance, mutual fidelity and commitment and also enable the expansion of autonomy of individuals and establish a sense of community, which is around the food. In this study, we have identified three specific elements that contribute to the effectiveness of the process: the way of producing food, as opposed to traditional agriculture, the shortening of chain and the activities in group promoted by the group of farmers and consumers. Thus, the Community-Supported Agriculture is a countermovement to the commodification in agriculture and an effective alternative in the construction of autonomy of those who are part of this net of food and in the expansion of social cohesion. The results and conclusions presented throughout the dissertation are relevant since they contribute with new information and possibilities of actions to slowdown rural exodus, alleviate poverty, reduce public spending on health with a healthier diet, as well as to promote the development of initiatives to preserve the environment.

The thesis deals with economical and accounting results of the national airline operator of the Czech Republic, Czech Airlines, Inc. (further referred to as CSA), and the global economical crisis effect on airline operators. This crisis hit all sectors of economic activity, including air transport, in the years 2008-2009. The main objective of this thesis is an evaluation of the anti-crisis measures CSA adopted during the last 5 years and its impact on the company's economy, especially on the operating income or operating loss which managed to be 3.7 billion Kc in 2009. The thesis is divided into three chapters. The first chapter is dedicated to basic characteristics of CSA, specifically its historical development, transport net progress and the current position of CSA on the air transport market. The second chapter talks about the operational and economical situation at CSA and the third chapter explains reclassification activities of CSA and its attempts for recovery.

本研究是針對內部控制自行評估（CONTROL SELF-ASSESSMENT簡稱CSA） 探討由理論到實際的實行的每一個階段的重點：為什麼需要CSA的概念？CSA的架構及方法為何？CSA實行的方法？ 以及CSA在美國實行的情形？希望藉由本項研究所得出來的概念，不但揭開CSA的面紗，更期望能幫助各公司能藉著CSA結合績效風險管理、目標管理達到其營運、財務、法令遵行的效果及效率。 本論文之研究程序為： （一） 收集國內外有關自行評估內部控制的文獻及法令，並探索自行評估內部控制的由來、實行的必要的理由，CSA的過程中內部稽核角色如何轉變及如何與內控理論的本意配合。 （二） 收集國外實行內控的最佳實例並在每種實行方法下，選出一家代表性的個案。 （三） 分析所選出的實例，並分析每個個案所實行的特色及成果。 （四） 歸納出各種實行方法的適用性及優缺點。 目 錄 圖次……………………………………………………………………2 表次……………………………………………………………………3 第一章緒論 4 第一節 研究背景及研究目的 4 第二節 研究方法 7 第三節 論文架構及大綱 11 第二章 內部控制制度概述 12 第一節 內部控制的定義及種類 12 第二節 內部控制制度的組成要素 15 第三節 企業目標與組成要素間的關係 21 第四節 與企業內部控制制度關聯之團體 23 第三章自行評估內部控制制度概念（簡稱CSA）之探討 29 第一節 CSA的定義及要素 29 第二節 CSA之必要性 31 第三節 實行CSA的三種模式 34 第四節 CSA的關鍵成功要素 38 第五節 CSA對稽核角色的影響 40 第四章 自行評估內部控制個案分析 42 第一節J C PENNY個案分析 42 第二節MAPCO公司個案分析 52 第三節CENTERIOR ENGERY個案分析 56 第四節 個案實施成果的分析 69 第五章結論與建議 76 第一節研究結論 76 第二節研究建議 79 第三節未來研究方向 79

La CsA és un potent immunosupressor àmpliament utilitzat en el trasplantament d'òrgans sòlids que com a principal efecte secundari mostra una elevada toxicitat renal que pot conduir a la pèrdua de la funció renal (Borel J.F. et al., 1976; Bennet W.M. et al., 1983). Els mecanismes moleculars pels quals la CsA exerceix els seu efecte immunosupressor han estat ben estudiats (Schreiber S.L., 1991; Liu J. et al., 1992), no obstant poc es coneix dels mecanismes d'acció a nivell molecular implicats en el dany renal. El tractament de cèl·lules PCT3 i HK-2 amb dosis creixents de CsA (desde 0 fins a 20 µM) demostra que la concentració de 10 µM és una dosi crítica a partir de la qual es posen de manifest varis esdeveniments cel·lulars tals com la disminució de la viabilitat cel·lular de manera dosi i temps dependent, la mort cel·lular per apoptosi, la disminució de la respiració mitocondrial i del percentatge de cèl·lules en fase S. Mitjançant un estudi proteòmic diferencial entre cèl·lules control i cèl·lules tractades amb la dosi 10 µM de CsA s'identifiquen putatius marcadors que ens permeten distingir la toxicitat renal creada per la CsA de la resta de símptomes de la nefropatia crònica i determinar l'evolució del dany renal causat per la CsA per tal de poder ajustar el tractament amb dosis de CsA que no siguin tòxiques. Les ciclofilines són una família de proteïnes expressades de forma ubiqua que posseeixen activitat peptidil-prolil cis/trans isomerasa i que s'uneixen selectivament al fàrmac immunosupressor CsA. La disminució de l'expressió de les ciclofilines mitjançant RNA d'interferència demostra una davallada de la sensibilitat cel·lular al tractament amb CsA. L'anàlisi proteòmic realitzat entre cèl·lules amb una de les dues ciclofilines silenciades gènicament i cèl·lules sense interferir ens ha de permetre esbrinar la participació de la CsA, les ciclofilines A i B o be l'activitat PPIasa d'aquestes en la toxicitat renal. / The use of CsA as a potent immunosuppressant has been limited by its severe nephrotoxic effects. The mechanisms involved are hemodynamic but also related with direct toxic effects of CsA on proximal tubule epithelial cells.CsA-induced toxicity analyses revealed that 10 µM CsA for 24h was the threshold condition to induce significant changes in cell viability and proteomic profile. At this concentration also appears apoptosis, decrease the percentage of cells in S phase and oxygen consumption.By means of high-throughput differential proteomic analyses and mass spectrometry techniques, we identified 38 differentially-expressed proteins on CsA-treated mouse PCT3 and human HK-2 cells, related to protein metabolism, response to damage, cell organization and cytoskeleton, energy metabolism, cell cycle and nucleobase/nucleoside/nucleotidic metabolism. Proteins identified in this work might be useful markers to eventually distinguish CsA toxicity from chronic allograft nephropathy in protocol biopsies of transplanted patients, facilitating the adjustment of CsA doses to non-toxic ranges, as well as, to study the impact of potential therapeutic interventions in an animal model. Cyclophilins are a family of proteins that posses peptidil prolil cis-trans isomerase activity and bind selectively at the immunosuppressant drug CsA. When we decrease the expression of the cyclophilin A or B by RNA interference techniques we observe that the cells are less sensible to CsA citotoxicity. Proteomic analysis between cells with cyclophilin A or B interfered and wild type cells will reveal the role of CsA, cyclophilins and the PPIase activity in the nephrotoxicity.

Syftet med studien var att undersöka förekomsten av sexuella övergrepp hos kvinnor inom den frivilliga missbruksvården samt beskriva kvinnornas situation utifrån utvalda livsområden. Studien bygger på material hämtat från DOK:s inskrivningsintervju 2007. Urvalet bestod av kvinnor inom den frivilliga missbruksvården som genomfört långa inskrivningsintervjun i DOK. Resultatet visade att 31,3 % av kvinnorna i undersökningsgruppen hade svarat ja på frågan om de varit utsatta för sexuellt övergrepp innan missbruksdebuten. Vid en jämförelse mellan kvinnor som varit utsatta för, respektive inte varit utsatta för sexuella övergrepp innan missbruksdebuten, visade resultatet att gruppen som varit utsatta hade sämre förhållanden inom flera livsområden samt ett tyngre missbruk jämfört med gruppen som inte varit utsatta. En slutsats som kan dras är att det är viktigt att vara medveten om att kvinnor inom missbruksbehandling kan ha flera problem än bara missbruket, medvetenheten gör det möjligt att erbjuda en bättre behandling för de här kvinnorna.