Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases, are small signaling molecules and critical in the regulation of many cellular processes including cell migration, growth via the endocytic pathway. This research involves the role of Rab GTPases, specifically Rab5 and its guanine exchange factors (GEFs), in the promotion of cancer cell migration and invasion. Two important questions abound: Are IGFR stimulation and downstream effect involved the endocytic pathway in carcinogenesis? What role does Rab5 play in cell migration and invasion of cancer cells? The hypothesis is that growth factor signaling is dependent on Rab5 activity in mediating the aggressiveness of cancer cells. The goal is to demonstrate that IGF-1 signaling is dependent on Rab5 function in breast cancer progression. Here, the results thus far, have shown that while activation of Rab5 may mediate increased cell proliferation, migration and invasion in breast cancer cells, the Rab5 GEF, RIN1 interacts with the IGFR thereby facilitating migration and invasion activities in breast cells. Furthermore, endocytosis of the IGFR in breast cancer cells seems to be caveolin dependent as the data has shown. This taken together, the data shows that IGF-1 signaling in breast cancer cells relies on IGF-1R phosphorylation, caveolae internalization and sequestration to the early endosome RIN1 function and Rab5 activation.

Conjugated Polymer Nanoparticles for Biological Labeling and Delivery

Cancer remains one of the world’s most devastating diseases, with more than 10 million new cases every year. However, traditional treatments have proven insufficient for successful medical management of cancer due to the chemotherapeutics’ difficulty in achieving therapeutic concentrations at the target site, non-specific cytotoxicity to normal tissues, and limited systemic circulation lifetime. Although, a concerted effort has been placed in developing and successfully employing nanoparticle(NP)-based drug delivery vehicles successfully mitigate the physiochemical and pharmacological limitations of chemotherapeutics, work towards controlling the subcellular fate of the carrier, and ultimately its payload, has been limited. Because efficient therapeutic action requires drug delivery to specific organelles, the subcellular barrier remains critical obstacle to maximize the full potential of NP-based delivery vehicles. The aim of my dissertation work is to better understand how NP-delivery vehicles’ structural, chemical, and physical properties affect the internalization method and subcellular localization of the nanocarrier. In this work we explored how side-chain and backbone modifications affect the conjugated polymer nanoparticle (CPN) toxicity and subcellular localization. We discovered how subtle chemical modifications had profound consequences on the polymer’s accumulation inside the cell and cellular retention. We also examined how complexation of CPN with polysaccharides affects uptake efficiency and subcellular localization. This work also presents how changes to CPN backbone biodegradability can significantly affect the subcellular localization of the material. A series of triphenyl phosphonium-containing CPNs were synthesized and the effect of backbone modifications have on the cellular toxicity and intracellular fate of the material. A mitochondrial-specific polymer exhibiting time-dependent release is reported. Finally, we present a novel polymerization technique which allows for the controlled incorporation of electron-accepting benzothiadiazole units onto the polymer chain. This facilitates tuning CPN emission towards red emission. The work presented here, specifically, the effect that side-chain and structure, polysaccharide formulation and CPN degradability have on material’s uptake behavior, can help maximize the full potential of NP-based delivery vehicles for improved chemotherapeutic drug delivery.

Androgyny versus Patriarchy: A Historicist‐Psychoanalytic Reading of Hemingway's The Garden of Eden and Wilkie Collins's The Woman in White

This paper will examine how male and female character interactions in Ernest Hemingway’s The Garden of Eden and Wilkie Collins’s The Woman in White expose the internalization, normalization, and perpetuation of current modes of patriarchy in terms of gender roles through their presentations of androgyny. This paper highlights the parallels of gender construction and the interaction within the social relations depicted in these two novels, which have not been compared previously. The premise, based on the psychoanalytic theories of Jacques Lacan and cultural materialism of Raymond Williams, is that fiction reflects historical and contemporary social relations. Lacanian and feminist interpretations have both been conducted on literature written by Collins and Hemingway; however, neither look at these particular novels as two examples for the same contemporary phenomenon of 21st century patriarchal interpellation. This paper most similarly follows the work of Slavoj Žižek who analyzes contemporary social relations through film (including classics such as Casablanca and works by Alfred Hitchcock) and other aspects of popular culture. This project’s contribution and uniqueness lie with the way it applies theory to these particular literary works, specifically concerning gender relations and the prevalence of androgyny in widely read works by well-known authors in two very different literary and historical eras. My interpretation of these two novels provides an evaluation of historical and contemporary patriarchal norms and a radical potentiality for subverting the idea of static gender roles that has remained prevalent throughout the three centuries of these texts’ existence.

HIV/AIDS: um perfil epidemiológico do vírus e uma análise das práticas seguras, conhecimento e percepção de mulheres

In recent decades, the debate surrounding the consequences of the HIV has passed by great changes. Earlier, prevention campaigns focused risk groups then risk behaviors and ultimately vulnerability. Furthermore, over the years, the dimensions of HIV that emerged in the social environment are these: internalization, heterosexualization, impoverishment and feminization. Based on these contexts, the composition of this study comprises two papers: the former has the overall objective to analyze the epidemiology and incidence of HIV in Brazilian regions in the period from 1980 to 2012; the latter, it aims to find out whether there is the relationship among safe practices, knowledge and perception of women residents in Manaus and Boa Vista cities on the infection by HIV. In paper 1, it was used information from the Health Ministry, as a data source. Besides, it was developed an exploratory and spatial analysis of incidence rates and relative proportion of notified cases. In paper 2, was used as a source of data, the research "Evaluating the process of spatial and epidemic diffusion of HIV in the federal units of Brazil-Northern Region" in 2008. Furthermore, Statistical Techniques of Cluster Analysis, Analysis of Variance, Chi-Square and Logistic Regression were applied. In this paper, it was found that, in Brazilian Regions, the prevalence of reported cases occurred among heterosexuals in men 20-40 year age group and residing in metropolitan areas. It was observed a significant spatial correlation of the incidence rate of reported cases of HIV. It was also noted by the results that have good knowledge and awareness about HIV does not imply, essentially, in a safe sexual intercourse. These results have shown the need public policies geared to the guiding of society, based in educational strategies aiming both information about the virus and its prevention, as well as public awareness for safe sex practices or in stable or not intercourses

A tributação como instrumento de proteção ambiental no Brasil

The Federal Constitution of 1988 gave special treatment to the issue of the environment, raising this diffuse right to the status of a fundamental right. In order to preserve it, the constitutional order is provided with various means to this purpose, including the possibility of using taxation. Several principles both constitutional, as infraconstitucional, support the use of taxation as a legal instrument to protect the environment. There is an intense legal debate about the suitability, characteristics, purposes and principles which underlie and restrict the environmental taxation. Discussions and proposals for reform of the tax system in order to include the ecological aspect at its core have been developed. The use of taxation as a way to fund public expenditures related to environmental causes, promote the internalization of negative externalities and as a way to induce behavior to benefit the environment finds support in the Brazilian legal system. This paper seeks to demonstrate that the national tax system is fully able to act as a tool available to the state for the implementation of the fundamental right to an ecologically balanced environment, whether through the taxes fiscal role or due, mainly, through the phenomenon of extrafiscality. Also, it is intended, through doctrinal, jurisprudential analysis and concrete cases, to investigate whether the tax system can be effective in protecting the environment in the way it is currently constructed, or if there is need to proceed with changes in its structure in order to achieve this goal

Estrutura e desempenho organizacional: uma análise na Universidade Federal do Rio Grande do Norte

This research analyses the components of the organizational structure of the UFRN (Rio Grande do Norte Federal University) and to what extent they affect organizational performance. The study, classified as exploratory and descriptive, was conducted in two phases. The first phase consists of a pilot test to refine the research instrument and to identify the latent components of the organizational structure, and the second to characterize these components and thereby establish relationships with organizational performance. In the first phase, the research was conducted in 20 UFRN organizational units with the participation of 84 employees between technical-administrative and teachers, after considering missing values and outliers, while the second phase occurred in two stages: one conducted with 279 valid cases, consisting of technical-administrative and teachers of 37 UFRN units, and another with 112 managers of the institution in the 49 units identified in this research. The instrument adopted in the first phase was composed of 36 indicators of organizational structure, with six extracted and adapted from the instrument developed by Medeiros (2003) and 30 prepared based on the literature review, from Mintzberg (2012), Hall (1984), Vasconcellos and Hemsley (1997) and Seiffert and Costa (2007) and 7 performance indicators adapted from Fleury and Mills (2006), Vieira and Vieira (2003) and Kaplan and Norton (1997) from the self-assessment instrument in use by the university. In this stage the data were analyzed using the techniques of factor analysis and reliability analysis by means of Cronbach’s alpha, aiming to extract the factors representing the components of the organizational structure. In step 1 of the second phase, the instrument, refined and reduced in the previous phase, with 24 variables of organizational structure and 6 for performance was used, while in step 2, a semi-structured interview guide with questions, organized into nine organizational structure elements, was adopted aiming to gather information to understand the relationship of structure to performance of the UFRN. The techniques used in the second phase, as a whole, were factor analysis and reliability analysis to characterize the components extracted in the previous phase and to validate the performance variables and correlation analysis, regression and content analysis to establish and understand the relationship between structure and performance. The results showed, in the two stages, six latent components of organizational structure in the context under study: training and internalization, communication, hierarchy, decentralization, formalization and departmentalization - with high levels of Cronbach's alpha indexes - which can thereby be characterized as components of UFRN structure. Six performance indicators were validated in this study, showing them as efficient and highly reliable. Finally, it was found that the formalization, communication, decentralization, training and internalization components positively affect UFRN performance, while departmentalization has an adverse affect and hierarchy did not show a significant relationship. The results achieved in this work are important in future studies to support the development of a model structure that represents the specifics of the university

Estratégias de enfrentamento de pessoas vivendo com AIDS frente à situação da doença

The Acquired Immune Deficiency Syndrome (AIDS), considered today one chronic nature of the disease due to the advent of antiretroviral therapy (TARV), brings to individuals living with this disease, difficulties related to social interaction and adaptation to new physical condition and the routines imposed by the treatment. This reality has a strong impact on the lives of these people in order of overcoming them use coping strategies, Coping. In this context, the aim of this study was to characterize the epidemiological, clinical and life habits of people living with AIDS and analyze the coping strategies used with the situation of the disease, according to sociodemographic, clinical and life habits. This is a cross-sectional study with a quantitative approach. The sample consisted of 331 people registered at the clinic of the Hospital Giselda Trigueiro (HGT), located in Natal / RN, who had scheduling for outpatient medical consultation from January to August 2014. The study was approved by the Ethics Committee the Federal University of Rio Grande do Norte with the Presentation of Certificate for Ethics Assessment (CAAE), paragraph 16578613.0.0000.5537. The data of social characterization showed predominance of men (52%), young people (42%) coming from the capital (58%), mulatto (53%), single (56%), heterosexual (79%), poor (68 %). With regard to clinical aspects it has been found that most held the first HIV testing for less than five years (60%) had signs and symptoms of AIDS before the examination (90%) were hospitalized (90%) started ART for less than five years (60%) believe they have good knowledge of the disease (75%) and believe that their health has improved (92%). For lifestyle, it became clear that most do not consume alcohol (71%), do not smoke (88%) and do not use illicit drugs (92%) and never used condoms before diagnosis (62%) and only 192 (58%) use the currently codon. With regard to the reference was higher coping focused modes of emotion, although the problem solving has been the second most common. The mean scores of women, workers, religious and never abandoned the treatment were higher for all factors. Having a partner, living with family members and support in the treatment had higher average scores for various factors, coinciding in the confrontation, withdrawal and social support. As for the leisure and physical exercise also dominated the modes focused on emotion as was seen in the correlation between the time of treatment, education and family income and IEEFL factors, although with low intensity. The profile of the study population confers with national characteristics, suggesting feminization, internalization, pauperization, heterosexual, increased CD4 cell count and viral load reduction during treatment and maintaining healthy lifestyle habits. Coping strategies used were more focused on emotion. In this context, it is understood that the identification of these strategies can facilitate care planning, encouraging such persons to adapt to stressors with the situation of the disease

Escrita colaborativa com google docs: flash fiction, noticing e aprendizagem de inglês como L2

Google Docs (GD) is an online word processor with which multiple authors can work on the same document, in a synchronous or asynchronous manner, which can help develop the ability of writing in English (WEISSHEIMER; SOARES, 2012). As they write collaboratively, learners find more opportunities to notice the gaps in their written production, since they are exposed to more input from the fellow co-authors (WEISSHEIMER; BERGSLEITHNER; LEANDRO, 2012) and prioritize the process of text (re)construction instead of the concern with the final product, i.e., the final version of the text (LEANDRO; WEISSHEIMER; COOPER, 2013). Moreover, when it comes to second language (L2) learning, producing language enables the consolidation of existing knowledge as well as the internalization of new knowledge (SWAIN, 1985; 1993). Taking this into consideration, this mixed-method (DÖRNYEI, 2007) quasi-experimental (NUNAN, 1999) study aims at investigating the impact of collaborative writing through GD on the development of the writing skill in English and on the noticing of syntactic structures (SCHMIDT, 1990). Thirtyfour university students of English integrated the cohort of the study: twenty-five were assigned to the experimental group and nine were assigned to the control group. All learners went through a pre-test and a post-test so that we could measure their noticing of syntactic structures. Learners in the experimental group were exposed to a blended learning experience, in which they took reading and writing classes at the university and collaboratively wrote three pieces of flash fiction (a complete story told in a hundred words), outside the classroom, online through GD, during eleven weeks. Learners in the control group took reading and writing classes at the university but did not practice collaborative writing. The first and last stories produced by the learners in the experimental group were analysed in terms of grammatical accuracy, operationalized as the number of grammar errors per hundred words (SOUSA, 2014), and lexical density, which refers to the relationship between the number of words produced with lexical properties and the number of words produced with grammatical properties (WEISSHEIMER, 2007; MEHNERT, 1998). Additionally, learners in the experimental group answered an online questionnaire on the blended learning experience they were exposed to. The quantitative results showed that the collaborative task led to the production of more lexically dense texts over the 11 weeks. The noticing and grammatical accuracy results were different from what we expected; however, they provide us with insights on measurement issues, in the case of noticing, and on the participants‟ positive attitude towards collaborative writing with flash fiction. The qualitative results also shed light on the usefulness of computer-mediated collaborative writing in L2 learning.

Química em cena: uma proposta para formação inicial de professores de química

In educational observed difficulty in train teachers to meet the medium and higher education needs, and one reason for this is the different experiences in the training of educators in relation to those found in the classroom. So often arise criticisms related to relevance and efficiency of degree courses, as regards the performance of its natural mission, which weakens the teacher training. Thus, improving the quality of education is very dependent on the initiatives of teachers, creating teaching alternatives to strengthen their performance in school. From this reflection, it is concluded that teacher training needs new educational proposals that qualify, and so can promote the formation of his students more adequately. Among the educational proposals as alternatives to initial teacher training may use the scientific theater (TC). Considering this possibility, this work has been proposed as investigate and discuss the influence of TC combined with experimentation in the initial training of future teachers in Chemistry who participate in the Groups Fanatics chemistry Theatre (UERN) and Chemistry on Stage (UFRN). Therefore, there was, in a first stage, theatrical essays based on the theater of the oppressed, and written dramaturgical scripts, a collaborative proposal. To incorporate experimentation in chemistry to theater rehearsals, there was a systematic literature search and after content analysis, were selected categories, materials and reagents easily accessible, easy procedures and implementation with low risk of accidents and easy care chemical waste. In the second part we identified: a) the beliefs of student teachers in the use of TC ally trial for initial training of chemistry teachers; b) the influence of TC ally to trial on learning of chemical concepts of high school students who attended the shows; c) the reasons for using or not TC ally to trial by chemistry teachers who participated in the TC group and currently work in the classroom. In this study, questionnaires and interviews were used, compounds, respectively, by a Likert scale and open questions. Quantitative data were analyzed by classical statistics the media, using as centrality measures the average, the concordance argument and the average deviation. Qualitative data were discussed according to content analysis, with categories that emerged from reading the answers. These analyzes concluded that the licensees have a positive view on the use of scientific theater for disclosure of the chemical for use in the learning of chemical concepts, pedagogical and disciplinary knowledge, and to form promotion strategy for research and extension at the University. They credit improvements in their initial training on the use of scientific theater combined with experimentation. The TC provides motivation for the construction of conceptual thinking in an informal way of chemical communication, allowing the student to expand their knowledge, not only favoring the phenomenological approach, but also the construction of chemical knowledge and the internalization of scientific concepts.

A ribeira da discórdia: terras, homens e relações de poder na territorialização do Assu colonial (1680-1720)

The internalization process of the Portuguese possession in Northern Captaincies - after the Dutch eviction and the development of activities related to livestock in the backlands (Sertão) – expanded the Portuguese territory in America. This process resulted in the advancement of Portuguese conquest over the region and conflicts involving agents of colonization and indigenous groups who inhabited that space, as well as conflicts of interest of captaincy’s major social groups and the defense policies of the Portuguese territory possession. Among the rivers which run through Rio Grande captaincy’s territory, the Açu was the one that aroused conquerors and colonizers of the back lands interest, making that spatiality an area where interest and power exercises converged and generated discord. This research aims to analyze the territorial process of Assu backlands, from the pioneers, conquerors and colonizers action over the space studied, during the event known as the War of the Barbarians in Assu, conflict that ensured the integration of the area the territory and the wishes of the Portuguese crown. Thus, it will be taken as objects of study social phenomena that characterized Assu’s riverside - at the turn of the 17th to the 18th century, in a cutout that extends from 1680 to 1720 - as an area of conflicts of interest, noticeable for analysis from period documents such as records of land grants concessions, correspondence between colonial and kingdom authorities, documents from the exercise of administration of Portuguese America and legislation.

A ribeira da discórdia: terras, homens e relações de poder na territorialização do Assu colonial (1680-1720)

The internalization process of the Portuguese possession in Northern Captaincies - after the Dutch eviction and the development of activities related to livestock in the backlands (Sertão) – expanded the Portuguese territory in America. This process resulted in the advancement of Portuguese conquest over the region and conflicts involving agents of colonization and indigenous groups who inhabited that space, as well as conflicts of interest of captaincy’s major social groups and the defense policies of the Portuguese territory possession. Among the rivers which run through Rio Grande captaincy’s territory, the Açu was the one that aroused conquerors and colonizers of the back lands interest, making that spatiality an area where interest and power exercises converged and generated discord. This research aims to analyze the territorial process of Assu backlands, from the pioneers, conquerors and colonizers action over the space studied, during the event known as the War of the Barbarians in Assu, conflict that ensured the integration of the area the territory and the wishes of the Portuguese crown. Thus, it will be taken as objects of study social phenomena that characterized Assu’s riverside - at the turn of the 17th to the 18th century, in a cutout that extends from 1680 to 1720 - as an area of conflicts of interest, noticeable for analysis from period documents such as records of land grants concessions, correspondence between colonial and kingdom authorities, documents from the exercise of administration of Portuguese America and legislation.

Escravo moderno em discurso: figuras de ação e ação em discurso nas representações do agir humano

This work has as object of study a social practice: modern slavery of workers in the sugar cane, and aims to present a reflection on maintenance, eradication or modification of this practice. This reflection bases itself upon the concepts of discourse advocated by Critical Discourse Analysis (Fairclough, 2001, 2003, 2006 and Chouliaraki; Fairclough, 1999) associated with Sociodiscursive Interactionism (Bronckart, 1999, 2006, 2008), and the concept of action figures, proposed by Bulea (2010). We follow the five steps outlined in Chouliaraki and Fairclough (1999): a) emphasis on a social problem, b) introduction and discussion of obstacles to tackle the problem, c) considerations concern the problem in practice d) identifying possible ways to past the obstacles, and e) reflection about the analyst role within the problem. In order to achieve step (b) in its discourse materiality axis, it has been identified the thematic content, discourse types, enunciative mechanisms and action figures of testimonials of sugar cane workers and other subjects involved with the problem in the documentaries Bagaço (2006, and Tabuleiro de Cana, Xadrez de Cativeiro (2006). These documentaries bring to the screen a little of sugar cane workers reality within an overexploitation, human rights disrespects and forced work. The analysis of textual/discursive aspects of testimonials has shown the ways in which the (de)construction of the representation of sugar cane action allows understanding of how the problem emerges and how it is rooted in the organization of social life. The general result of this reflection point to the internalization of social practices deep-rooted in evaluations of the sugar cane worker subjective world and from social world values, opinions and rules. The results also show that, in their discourse, workers assume their slavery sometimes consciously, sometimes unconsciously, but only suggest a reaction against the oppression imposed on them because they have internalized and naturalized their enslavement.

Escravo moderno em discurso: figuras de ação e ação em discurso nas representações do agir humano

This work has as object of study a social practice: modern slavery of workers in the sugar cane, and aims to present a reflection on maintenance, eradication or modification of this practice. This reflection bases itself upon the concepts of discourse advocated by Critical Discourse Analysis (Fairclough, 2001, 2003, 2006 and Chouliaraki; Fairclough, 1999) associated with Sociodiscursive Interactionism (Bronckart, 1999, 2006, 2008), and the concept of action figures, proposed by Bulea (2010). We follow the five steps outlined in Chouliaraki and Fairclough (1999): a) emphasis on a social problem, b) introduction and discussion of obstacles to tackle the problem, c) considerations concern the problem in practice d) identifying possible ways to past the obstacles, and e) reflection about the analyst role within the problem. In order to achieve step (b) in its discourse materiality axis, it has been identified the thematic content, discourse types, enunciative mechanisms and action figures of testimonials of sugar cane workers and other subjects involved with the problem in the documentaries Bagaço (2006, and Tabuleiro de Cana, Xadrez de Cativeiro (2006). These documentaries bring to the screen a little of sugar cane workers reality within an overexploitation, human rights disrespects and forced work. The analysis of textual/discursive aspects of testimonials has shown the ways in which the (de)construction of the representation of sugar cane action allows understanding of how the problem emerges and how it is rooted in the organization of social life. The general result of this reflection point to the internalization of social practices deep-rooted in evaluations of the sugar cane worker subjective world and from social world values, opinions and rules. The results also show that, in their discourse, workers assume their slavery sometimes consciously, sometimes unconsciously, but only suggest a reaction against the oppression imposed on them because they have internalized and naturalized their enslavement.

Internacionalização de empresas e o fechamento do capital : um estudo sobre a deslistagem no mercado brasileiro

This work contributes to the finance literature proposing to analyze the relationship between the degree of internationalization of Brazilian companies and the likelihood of delisting. Therefore, even though the internationalization as a differential, in the formulation of hypotheses and analysis of the relationship between the variables dealt with concepts and theories within the Corporate Governance, which is already established in theory when it comes to delisting. First, with a view to the theory of internalization, which gives competitive advantages to the company due the adoption internationalization strategy and in parallel to the positive effects that this strategy generates on firms performance, it was formulated an hypothesis that the degree of internationalization would be adversely related to the probability of delisting, mainly due to such benefits generated to the organization. In turn, as an alternative hypothesis of the research, it proposed a positive relationship between these variables, based on agency theory, according to which internationalization would contribute to delisting by increasing geographical separation between shareholders and managers and, consequently, agency conflicts and the difficulty of monitoring. For the achievement of objectives, as well as being included economic and financial variables and GC, it was proposed the analysis of periods of crisis, as the events of recent past of the Brazilian economy. Starting from a base model initially developed by Pour and Lasfer (2013), which later, the proxies of internationalization and crisis have been added also contemplating adjustments to the Brazilian context. The data collected include the period from 2006 to 2014 and information on active and inactive companies at Bovespa. As results, it was found negative significance between the degree of internationalization and the delisting decision, confirming the first hypothesis of the research and stating that the benefits generated by internationalization in the company generate it spreads and results that reduce the probability of delisting. By analyzing the results of control variables was still possible to observe that, even internationalization reducing the likelihood of delisting, by particular aspects of corporate governance in Brazil, such as the high ownership concentration, the benefits it generates contribute to delisting. Regarding the analysis in crisis, the consequences of the crisis of the US subprime in general market were more relevant that the occurrence of itself, unlike the Brazilian internal crisis of 2014, which was statistically significant for the analyzed event. For future researches it is suggested the expansion of database and individual treatment of the reasons adopted by a company when delisting decision.

Effet du CP-3(iv), un ligand du récepteur CD36, sur le stress oxydatif suite à une ischémie cardiaque transitoire chez la souris

Le récepteur éboueur CD36 facilite l’internalisation des acides gras libres non estérifiés (AGNE) au niveau des tissus cardiaque et périphériques. Lors d’une ischémie-reperfusion du myocarde (MI/R), les dommages produits sont en partie liés à l’internalisation des AGNE et à la production d’espèces réactives de l’oxygène, contrairement à ce qui est observé chez des souris déficientes en CD36 (CD36-/-). Nous avons émis l’hypothèse selon laquelle le CP-3(iv), un ligand synthétique du récepteur CD36, exercerait un effet cardioprotecteur en réduisant la taille de la zone myocardique infarcie lors d’une ischémie transitoire du myocarde. Nos objectifs étaient 1) de déterminer l’effet cardioprotecteur du CP-3(iv) et 2) de définir son mécanisme. Pour cela, des études in vivo et ex vivo ont été faites. Des souris de type sauvage ont été traitées avec le CP-3(iv) (289 nmol/kg) par voie sous-cutanée pendant 14 jours avant d’être soumises à 30 minutes d’ischémie suivant la ligature de l’artère coronaire gauche descendante et de sa reperfusion pendant une période de 6 ou 48 heures. De plus, des coeurs isolés de souris ont été perfusés 30 minutes, suivi de 40 minutes à faible débit (10%) et de 30 minutes de reperfusion pendant laquelle le coeur est perfusé avec le CP-3(iv) à une concentration de 10-6 M. Nos travaux ont montré que l’effet cardioprotecteur d’un traitement préventif par le CP-3(iv) permet de diminuer la taille de l’infarctus et préserve l’hémodynamie cardiaque de façon dépendante du CD36 puisque cet effet est non visible chez les souris CD36-/-. De plus, le CP-3(iv) exerce non seulement un effet systémique, mais aussi un effet cardioprotecteur direct sur le coeur isolé.