No description available.

No description available.

Diabetes mellitus tipo 1 resulta da produção insuficiente ou da ausência de insulina, decorrente da destruição de células β, por mecanismo auto-imune. O tratamento deste tipo de diabetes consiste na administração subcutânea de insulina exógena. Recentemente, foi demonstrado que o transplante de ilhotas pancreáticas é capaz de tornar o portador de diabetes tipo 1 independente de insulina exógena. Apesar do sucesso alcançado, a necessidade permanente de imunossupressão é uma das principais barreiras para que o transplante de ilhotas possa ser realizado em número maior de pacientes. Assim, o desenvolvimento de novas metodologias que evitem a rejeição do enxerto, como o macro e o microencapsulamento de ilhotas, continua sendo crucial para o estabelecimento definitivo do transplante de ilhotas como opção terapêutica no tratamento de diabetes tipo 1. Neste trabalho, foi padronizado um modelo animal para avaliar, in vivo, a funcionalidade das ilhotas pancreáticas humanas isoladas e purificadas na Unidade de Ilhotas Pancreáticas Humanas do IQUSP. Ratos NIH nude foram tornados diabéticos através de injeção de estreptozotocina para o implante de ilhotas pancreáticas humanas nuas e microencapsuladas. As ilhotas foram microencapsuladas em Biodritina, um novo heteropolissacarídeo patenteado e cedido ao nosso laboratório, tendo sido possível padronizar a produção de microcápsulas uniformes e homogêneas, com tamanho médio entre 400µm e 600 µm. A reversão do diabetes ocorreu em 24% dos ratos nude transplantados com ilhotas pancreáticas humanas nuas. Por outro lado, não observamos reversão do diabetes quando ilhotas encapsuladas foram implantadas, apesar do teste de atividade funcional realizado in vitro ter demonstrado que elas continuam a secretar insulina e a responder ao estímulo com glicose após o encapsulamento. Para elucidar este efeito, cápsulas vazias foram implantadas em ratos nude e em ratos imunocompetentes, os quais desenvolveram processo inflamatório acompanhado de processo fibrótico no local do implante. Estudo imuno-histoquímico está sendo realizado para esclarecer a natureza e a intensidade destes processos. / Type 1 diabetes mellitus results from insufficient or absence of insulin production, as a consequence of destruction of pancreatic β cells, by an auto-imune mechanism. Treatment for this type of diabetes consists of subcutaneous administration of exogenous insulin. Recently, it has been demonstrated that pancreatic islet cell transplantation is capable of rendering type I diabetic patients independent of exogenous insulin. However, in spite of the success achieved, permanent immunosuppression is still required, being the main barrier to expand this treatment to a large number of patients. Therefore, development of new technologies, such as islet macro and microencapsulation to avoid rejection of the tissue implanted, is still crucial for definitive establishment of islet transplantation as a therapeutic alternative for type I diabetes. In the present work, an animal model was established for in vivo evaluation of the functional ability of human pancreatic islets, which were isolated and purified at the Human Pancreatic Islet Unit of the University of São Paulo Chemistry Institute. Diabetes was induced in NIH nude rats through streptozotocin injection followed by implantation of naked or microencapsulated human pancreatic islets. Biodritin, a new and patented heteropolyssaccaride was used to microencapsulate the islets. The production of uniform and homogeneous microcapsules with diameters in the range of 400µm e 600 µm was successfully established. Reversion of diabetes occurred in 24% of the nude rats transplanted with human pancreatic islets. On the other hand, no reversion of diabetes was observed when encapsulated islets were implanted, although their functional activity in vitro indicated that they secreted insulin and responded to glucose stimulation upon encapsulation. In order to elucidate this effect, empty capsules were implanted in nude rat and in immunocompetent rats, both of which developed an inflammatory process accompanied by a fibrotic process in the site of the implant. Immunohistochemical studies are underway to address the nature and the intensity of these inflammatory processes.

This essay examines the performance artworks Action Pants: Genital Panic (1969), Interior Scroll (1975) and S.O.S Starification Object Series (1974-82) by artists VALIE EXPORT, Carolee Schneemann and Hannah Wilke. The objective is to analyse the expressions of these artworks, from a theoretical viewpoint of feminist art-theoreticians and their critique regarding the female body in representation. Performance- and body-art have been the subject of discussion with respect to the female nude in the history of art, and the patriarchal structures that surround it. These eminent theories about the female body in art differ from one another, leaving this study to investigate given works and the explicit body-language that unites them, with the aim to identify a favourable representation of the female body in 1960sand 70s performance art with the vantage point of these artworks. The present essay has demonstrated that vaginal iconology exists in all works and can be presented in various ways. It becomes clear that the work of VALIE EXPORT provides a framework most suitable as a feminist, critical strategy to counteract the notion of the male gaze, framing, and representation of the body as commodity in capitalist-society. However, the works of Schneemann and Wilke, with more essentialist themes, can through ambiguity contribute to a positive representation of woman in representation. There is no simple answer to which way 2 of using the body is the most beneficial for feminism, however, a critical representation of the female body in performance and body art, in relation to the artists’ own intentions, creates positive ambiguity, thus these artworks do not only reinforce patriarchal conventions regarding the female body.

Diabetes mellitus tipo 1 resulta da produção insuficiente ou da ausência de insulina, decorrente da destruição de células β, por mecanismo auto-imune. O tratamento deste tipo de diabetes consiste na administração subcutânea de insulina exógena. Recentemente, foi demonstrado que o transplante de ilhotas pancreáticas é capaz de tornar o portador de diabetes tipo 1 independente de insulina exógena. Apesar do sucesso alcançado, a necessidade permanente de imunossupressão é uma das principais barreiras para que o transplante de ilhotas possa ser realizado em número maior de pacientes. Assim, o desenvolvimento de novas metodologias que evitem a rejeição do enxerto, como o macro e o microencapsulamento de ilhotas, continua sendo crucial para o estabelecimento definitivo do transplante de ilhotas como opção terapêutica no tratamento de diabetes tipo 1. Neste trabalho, foi padronizado um modelo animal para avaliar, in vivo, a funcionalidade das ilhotas pancreáticas humanas isoladas e purificadas na Unidade de Ilhotas Pancreáticas Humanas do IQUSP. Ratos NIH nude foram tornados diabéticos através de injeção de estreptozotocina para o implante de ilhotas pancreáticas humanas nuas e microencapsuladas. As ilhotas foram microencapsuladas em Biodritina, um novo heteropolissacarídeo patenteado e cedido ao nosso laboratório, tendo sido possível padronizar a produção de microcápsulas uniformes e homogêneas, com tamanho médio entre 400µm e 600 µm. A reversão do diabetes ocorreu em 24% dos ratos nude transplantados com ilhotas pancreáticas humanas nuas. Por outro lado, não observamos reversão do diabetes quando ilhotas encapsuladas foram implantadas, apesar do teste de atividade funcional realizado in vitro ter demonstrado que elas continuam a secretar insulina e a responder ao estímulo com glicose após o encapsulamento. Para elucidar este efeito, cápsulas vazias foram implantadas em ratos nude e em ratos imunocompetentes, os quais desenvolveram processo inflamatório acompanhado de processo fibrótico no local do implante. Estudo imuno-histoquímico está sendo realizado para esclarecer a natureza e a intensidade destes processos. / Type 1 diabetes mellitus results from insufficient or absence of insulin production, as a consequence of destruction of pancreatic β cells, by an auto-imune mechanism. Treatment for this type of diabetes consists of subcutaneous administration of exogenous insulin. Recently, it has been demonstrated that pancreatic islet cell transplantation is capable of rendering type I diabetic patients independent of exogenous insulin. However, in spite of the success achieved, permanent immunosuppression is still required, being the main barrier to expand this treatment to a large number of patients. Therefore, development of new technologies, such as islet macro and microencapsulation to avoid rejection of the tissue implanted, is still crucial for definitive establishment of islet transplantation as a therapeutic alternative for type I diabetes. In the present work, an animal model was established for in vivo evaluation of the functional ability of human pancreatic islets, which were isolated and purified at the Human Pancreatic Islet Unit of the University of São Paulo Chemistry Institute. Diabetes was induced in NIH nude rats through streptozotocin injection followed by implantation of naked or microencapsulated human pancreatic islets. Biodritin, a new and patented heteropolyssaccaride was used to microencapsulate the islets. The production of uniform and homogeneous microcapsules with diameters in the range of 400µm e 600 µm was successfully established. Reversion of diabetes occurred in 24% of the nude rats transplanted with human pancreatic islets. On the other hand, no reversion of diabetes was observed when encapsulated islets were implanted, although their functional activity in vitro indicated that they secreted insulin and responded to glucose stimulation upon encapsulation. In order to elucidate this effect, empty capsules were implanted in nude rat and in immunocompetent rats, both of which developed an inflammatory process accompanied by a fibrotic process in the site of the implant. Immunohistochemical studies are underway to address the nature and the intensity of these inflammatory processes.

New media technologies are changing the ways that we not only go about our day-to-day lives, but also the ways that we sell and exchange our labor within the capitalist economy. These technologies are shaping how we represent and perceive ourselves and others, as well as the ways in which, as we move about the world, our images are taken and circulated with neither our explicit permission, nor sometimes our knowledge (Dovey, 2000; Toffoletti, 2007). Despite the fact that we can no longer viably opt out of visual or technological culture, there remains a strong rhetoric of personal responsibility when such images are used in ways that are unexpected and sometimes extremely damaging (C. Hall, 2015). The growth in incidences of what Clare McGlynn (2017) calls “image-based sexual violence” cannot be divorced from the economic and cultural shifts that are both challenging and reifying dominant power relations in the early 21st century. This doctoral thesis examines the economic and social discourses underpinning news reporting on sexual privacy violations in relation to new media technologies and shifting forms of female celebrity. Using empirical methods to collect and sort U.S. and Canadian news articles at a macro level as well as discourse analysis of news reporting at the micro level, I focus on two particular sites wherein new media celebrity, sexual violence/violation, and political economies converge: the celebrity sex tape scandal and the stolen celebrity nude photo. I examine sexuality and privacy violation in an exemplary economic context, looking at how the “leaked” sex tape or image functions in the gendered sexual economy to undermine claims to meritocratic capitalist success. I focus on two moments of crisis: firstly, the pop culture crisis of 2007-2008, coinciding with the global economic recession as well as the growth in new media technology and social media usage, wherein several high-profile female celebrities undergo dramatic and very public “breakdowns” in proper femininity, ranging from the fairly banal “scandal” surrounding a then-15-year-old Miley Cyrus posing semi-nude for Vanity Fair to the more severe and illegal acts of Lindsay Lohan and Paris Hilton (both of whom were arrested for driving under the influence across this time period). Secondly, I examine the moment of crisis signaled by the 2014 iCloud hacking incident wherein hundreds of female celebrities’ personal private nude photos were stolen and circulated online. I analyze the sex “scandals” that are both discursively constructed by, and circulating through, the news at these moments. The findings point to several notable trends in the contemporary political climate. Firstly, they illuminate the tensions and contradictions in the media’s attempt to reconcile post-feminist sexual “empowerment” narratives with the broader imperatives of neoliberalism, surveillance, and self-commodification. Secondly, this thesis provides a timely analysis of the gendered pathways to success and the gatekeeping that is conducted both within and by the (news) media, which are themselves invested in narratives of meritocracy. Finally, the cynical, meta-commentary circulating in the news reporting on celebrity content – reporting that is increasingly beholden to corporate interests – contributes to the broader erosion of trust in mainstream media. In today’s media environment in particular, studies of heirs-turned-reality stars such as Paris Hilton (whose trajectory is eerily similar to that of U.S. President Donald Trump), are particularly urgent, as are studies that connect the seemingly disparate yet increasingly converging fields of celebrity, journalism, feminism (and sexual violence), and neoliberalism.

Endometriosis is a gynecological disease in which endometrial glands and stroma are present outside the uterus. Pelvic pain, infertility and decreased quality of life are the main problems caused by this disease carrying epidemiological and social impact. Peritoneal endometriosis which is characterized by the presence of red, black and white pelvic endometriotic lesions is clearly a multifactorial pathology associated with a local inflammatory response in the pelvic cavity. In vitro studies suggest that the transcription factor nuclear factor-kappaB (NF-êB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement and role of the NF-êB pathway in endometriosis in vivo. Firstly, NF-êB activation and intercellular adhesion molecule (ICAM)-1 expression were investigated in thirty-six peritoneal endometriotic lesions from women. Constitutive NF-êB activation, involving p65- and p50-containing dimers, was demonstrated in peritoneal endometriotic lesions by electrophoretic mobility shift assays and supershift analyses, as well as NF-êB (p65) DNA-binding activity immunodetection assays. NF-êB activation and ICAM-1 expression were significantly higher in red lesions than black lesions, while IêBá (NF-êB inhibitory protein) expression was constant, as shown by Western blot analyses. Secondly, endometriosis was induced in nude mice by intraperitoneal injection of fluorescent labeled menstrual endometrium. Two NF-êB inhibitors (BAY 11-7085 and SN-50) were injected intraperitoneally and endometriotic lesions were recovered on day 5. Both NF-êB inhibitors induced a significant reduction in lesion development compared to control mice. NF-êB activation and ICAM-1 expression of endometriotic lesions were significantly reduced in treated mice, and cell proliferation in BAY 11-7085-treated mice. Both inhibitors produced a significant increase in apoptosis of endometriotic lesions, as assessed by active caspase-3 immunostaining and the TUNEL method. In conclusion, this is the first study to show constitutive NF-êB activation in peritoneal endometriotic lesions collected from women and during the initial development of endometriotic lesions in an animal model. Differential levels of NF-êB activation have been established between red and black lesions, providing more evidence on the distinct inflammatory status of these two types of peritoneal endometriotic lesions. In addition, this study offers further insight into the pathways implicated in NF-êB activation in endometriotic lesions, showing the involvement of p50/p65 dimers and suggesting participation of the canonical pathway of NF-êB activation. This study also demonstrates, for the first time, that NF-êB inhibition reduces the initial development of endometriotic lesions by inhibiting the inflammatory response and cell proliferation, and inducing apoptosis of endometriotic lesions. The NF-êB pathway therefore looks to be a promising therapeutic target for endometriosis prevention and treatment.

Dietary factors may affect development and progression of prostate cancer. Experimental and epidemiological studies have suggested an effect of phytoestrogens on prostate cancer. Lignans are the predominant phytoestrogen in a Western diet. The effects of a diet rich in phytoestrogens and in particular lignans, as compared to a control diet, were assessed in several prostate cancer models. In paper I, 70 athymic nude mice with transplanted subcutaneous LNCaP tumours, an androgen sensitive human prostate cancer cell line, were fed one out of six phytoestrogen rich diets or a control diet after tumour injection. The rye diet, with high lignan content, decreased tumour take and growth, decreased secretion of prostate specific antigen and increased apoptosis. Addition of fat to the rye diet decreased the beneficial effects. In paper II, transgenic mice designed to develop prostate cancer (TRAMP) were fed rye bran or a control diet from the age of four weeks. Rye bran decreased prostate epithelial cell volume by 20%, and increased cell apoptosis by 31% as compared to the control diet. In paper III, we examined the effects of 7-hydroxymatairesinol (HMR), a purified lignan, in nude mice with subcutaneous LNCaP tumours in two different concentrations as compared to a control diet. Mice on the HMR diets had a reduced tumour take rate, lower total tumour volume, increased proportion of non-growing tumours, and increased apoptosis as compared to the control diet. Paper IV was a three week intervention study exploring the effects of rye bran bread vs. a control diet in men with prostate cancer. The men in the rye group had increased levels of plasma enterolactone and in biopsies from the prostate after the intervention an increase in apoptosis was observed in comparison with biopsies obtained before the intervention. In paper V, we examined the association between plasma levels of enterolactone, and risk of prostate cancer in a nested case control study. In the Northern Sweden Health and Disease Cohort, enterolactone concentrations were measured in plasma obtained at a mean time of 5 years before diagnosis from 265 cases of prostate cancer, and from 525 matched controls. We found no significant association between plasma enterolactone and risk of prostate cancer. Men with very low enterolactone levels (bottom decile) however, had significantly higher risk of prostate cancer. Phytoestrogen rich diet including soy, rye bran, substances purified from rye, and a purified lignan (HMR) all inhibited prostate tumour growth. However, it cannot be concluded that the effects observed were due solely to lignans as other components in rye grain such as tannins, phytic acid, ferulic acid, vitamins and minerals may have contributed to the beneficial effects. Thus, additional studies are needed to further elucidate the effects of phytoestrogens on prostate cancer development and progression.

Sex steroids are inevitable in women. However, long-term exposure to sex steroids increases the risk of breast cancer. A complete understanding of sex steroid control of the breast and how it relates to breast cancer risk is still lacking. Angiogenesis and proteolytic enzyme activity are crucial for the process by which tumors evolve into a vascularized, invasive phenotype. Matrix metalloproteinases are potent matrixdegrading enzymes that affect several steps in tumor progression including angiogenesis. In the female reproductive organs, sex steroids regulate angiogenesis and MMP activity, yet little is known how sex steroids affect these crucial events in normal and malignant breast tissue. This thesis elucidates a link between sex steroids, MMP activity, and angiogenesis. It is shown that estradiol down-regulates while tamoxifen up-regulates the protein expression and activity of MMP-2 and MMP-9 in human breast cancer cells in vitro and in human breast cancer xenografts in vivo. The results further suggest that a biological consequence of this regulation may be modulation of tumor angiogenesis. The net effect of adding tamoxifen to estradiol treatment was an increase in extracellular levels of the endogenous angiogenesis inhibitor endostatin and decreased levels of the tumor promoter TGF-β1 compared to estradiol treatment only. This was accompanied by reduced vasculature and decreased tumor growth. Similarly, a regulatory effect of estradiol and tamoxifen on endostatin generation was observed in normal human breast tissue by whole-tissue culture and microdialysis in human breast tissue in situ. In conclusion, the results presented in this thesis suggest previously unknown mechanisms of action of estradiol and tamoxifen in breast cancer and in normal human breast tissue, and novel means by which estradiol may tip the scale to favor angiogenesis. This knowledge may be important for the understanding of sex steroid dependent breast carcinogenesis and in the future development of tissue-specific preventive as well as therapeutic strategies against breast cancer.

The collection of paintings and drawings constituting the thesis exhibition The Anxious Actor are rooted within the visual language of contemporary realist figurative painting and drawing, with a focus on the male body. Traditionally in western culture, the depiction of the human form, both male and female, has sought to reinforce hierarchical constructions and meta-narratives implicit in religious and imperialistic structures. I paint and draw my own body as subject, exploring personal narratives that contradict these pre-existing notions. As a queer man interested in the vocabulary of realist figurative painting, my body is a catalyst for my fascination with stereotypic masculine portrayals.<p> Utilizing historic themes of male bravado, heroism and narcissism I juxtapose the mundane realities of everyday contemporary life. My narratives are situated within the complex visual languages of Neo-classical, Baroque, Rococo and Renaissance style painting. These specific pictorial vocabularies add both psychological and metaphoric weight to my conceptual process; locating my marginalized identity within historic and contemporary archetypes.