Made available in DSpace on 2014-06-11T19:28:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-28Bitstream added on 2014-06-13T20:38:00Z : No. of bitstreams: 1 azevedo_gmg_me_bauru.pdf: 447331 bytes, checksum: 3459a7a031014f04cb54cfe4ab25d645 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo investigou o vínculo mãe-bebê a partir do relato das mães, bem como as relações fraternais e os conflitos edípicos de crianças com psoríase em atendimento ambulatorial no Instituto Lauro de Souza LIma - Bauru, com base no referencial psicanalítico. A psoríase é uma doença crônica de pele, acomete de 1 a 3% da população e tem etiologia indefinida, embora fatores genéticos, ambientais e psicológicos sejam apontados como fazendo parte do quadro etiológico da doença. A literatura demonstra relações entre eventos emocionalmente traumáticos e o aparecimento ou agravamento de fenômenos psicossomáticos, entre eles a psoríase. A pele, como o maior órgão do corpo humano, serve de barreira de contato entre o indivíduo e o meio externo. É apontado como local onde são vivenciados os primeiros contatos com o mundo externo e constitui importante via corporal de formação e desenvolvimento do ego infantil. A pele representa uma divisa entre o mundo interno e o externo, ao mesmo tempo em que faz a ligação entre o indivíduo e o meio. Buscou-se estudar as relações de crianças com psoríase com suas mães e familiares, visando identificar possíveis relações compreensivas entre características dos vínculos e a doença dermatológica. Participaram do estudo 6 crianças com psoríase e suas mães, as crianças tinham entre sete e dez anos de idade. Foi realizada entrevista semi-estruturada para investigar o vínculo mãe-criança, com ênfase no vínculo primário mãe-bebê, uma vez que a literatura ressalta ser este o vínculo mais significativo para a construção da estrutura psíquica. Nas crianças, foi aplicado o Teste do Desenho da Família, visando identificar, pela interpretação dos aspectos emocionais projetados no desenho, como a criança se percebe no ambinte familiar, investigando... / The present study investigated the mother-child attachment, as well as the fraternal relationship and the Oedipus Complex conflicts of children with the diagnosis of psoriasis that were under treatment at the Lauro de Souza Lima Institution - Bauru - SP, based on the psychoanalytical referential. Psoriasis is a chronic skin disease that affects from one to three per cent of the world's population. The cause of psoriasis is undefined although ambient, genetics and psychological factors are considered to play a part in its etiology. Specific literature shows evidence of a connection between emotionally traumatic events and the outcome or worsening of psychosomatic disorders, among them psoriasis. The skin, as the biggest human organ, is used as a contact barrier between the organism and the external world, and is indicated as the local where the first contacts with the world are experienced. This study examined the relationship that children bearing psoriasis had with their family, especially with their mother, aiming to indicate possible comprehensive relations between the characteristics of familiar bonds and the dermatological disease. Six children, aging between seven and ten years, bearing psoriasis and their mothers took part of this work. The mothers were interviewed and the children were submitted to the Test of the Family Drawing. The results pointed out that the mother-baby attachment of all participants showed signs of difficulties in its early stages. As a result of this, mothers and children developed pathological bonds, with symbiotic characteristics. The children demonstrate strong conflicts with their brothers, sisters and parents. Besides, they showed strong guilty and separation anxiety, related to the mother, indicating repressed aggressive impulses.

A thesis submitted to the Faculty of Arts in fulfilment of the requirements for the Degree of Doctor of Philosophy in the Department of Psychology at the University of Zululand, South Africa, 2014 / This study involved an evaluation of an energy healing programme using participatory action research. The main research question related to the effectiveness of an energy healing programme in a group of psoriasis sufferers. The other research questions examined the participants‘ lived experiences of the programme; the extent to which awareness and intention to heal, as forms of energy, raised levels of consciousness and finally the extent to which new awareness led to corresponding bodily changes related to psoriasis. The study was based on the experiences of three participants living with psoriasis who participated in a five week energy healing programme. The sample was based on individuals living with psoriasis and with a shared interest in energy healing. Participants ranged between the ages of 24 and 54.Thegroup comprised one male and two females from a Hindu background, living in the greater Durban area. The programme involved the practice of various energy healing modalities that included the different forms of meditation, pranayama and yoga. The programme required weekly attendance at experiential group session with a duration of 90 minutes. An integrated methodological approach was used to capture the essence of energy healing through four ways of being and knowing. These included interior, exterior, individual and collective perspectives. A positivist research approach provided objective findings of heart rhythm coherence and quality of life measures on effectiveness of the energy healing programme. These findings showed a corresponding relationship with subjective data based on personal experiences of energy healing. First person perspectives included themes of self-discovery, self-acceptance, detached observing and improved relationships as it relates to higher states in consciousness. This study should be replicated on a larger scale using more controlled research methods to validate the use of energy healing as an adjunct treatment for people living with psoriasis.

Psoriatic disease (PD) is an autoimmune disease that affects millions of women and currently has no cure. Examining the lived experience of women with PD who choose to treat their disease with alternative methods may allow for deeper understanding of how mental health professionals can support their choices. Using phenomenology, this study looked at the experiences of these women through theories of self-efficacy and self-in-relation theory, theories that empower and speak to women. The participants consisted of women who reported a diagnosis of PD, who reported they had abstained from pharmaceutical interventions for at least the previous six months. The sample size consisted of 7 participants, recruited through social media, from various parts of the world. Explication was used to assess the data and consisted of the following: bracketing and phenomenological reduction, delineating units of meaning, clustering of units of meaning to form themes, summarizing each interview, and extracting general and unique themes from all interviews and making a composite summary. The findings of this study showed that the participants reported feeling capable of pursuing health options that aligned with their values and were not opposed to pharmaceutical options at some point. In addition, findings indicated participants felt minimal, if any, support from their medical care providers. The results of the study may facilitate positive social change by informing women with PD about the benefits of taking an active role in treatment planning. Further, this study'€™s results may expand knowledge about treatment of women with PD and inform medical professionals, specifically mental health professionals, about what is important to these women in terms of a treatment plan.

Dans le cadre de ce projet de maîtrise, le but principal était de poursuivre le développement d'un modèle de peau psoriasique reconstruit par génie tissulaire et de caractériser le rôle de l'innervation sensorielle dans le phénotype psoriasique de ces derniers. Le développement de cet équivalent vise avant tout à mieux comprendre la pathogénèse du psoriasis et potentiellement ouvrir la porte à de nouvelles voies thérapeutiques permettant de contrôler la maladie ou ses symptômes. Avec nos protocoles, nous avons pu démontrer que l'ajout d'innervation à un équivalent de peau reconstruit par génie tissulaire exacerbait le phénotype psoriasique en tout ou en partie. Jusqu'à présent, la caractérisation des cytokines étudiées dans nos protocole nous laisse croire que le facteur de croissance neuronal (NGF) est le principal médiateur de la prolifération kératinocytaire caractérisant les peaux psoriasiques.

Le psoriasis est une maladie auto-immune dont la cause, · toujours inconnue à ce jour, repose sur plusieurs mécanismes intercellulaires dont les interactions fonctionnelles entre les kératinocytes et les lymphocytes T. Notre modèle in vitro permet l' étude des interactions cellulaires en suivant l' analyse de la production de 22 cytokines/chimiokines ainsi que le changement en apoptose des cellules. Nous avons observé une sécrétion augmentée de plusieurs cytokines/chimiokines par les kératinocytes psoriasiques comparativement au kératinocytes sains. De plus, lors de la co-culture des lymphocytes T avec les kératinocytes, la production de plusieurs cytokines/chimiokines fût augmentée avec les kératinocytes psoriasiques comparativement aux kératinocytes sains. Une survie augmentée des lymphocytes T eh co-culture a également été observée. Ce modèle expérimental de co-culture témoigne des interactions fonctionnelles entre les kératinocytes et les lymphocytes T ainsi que de la persistance des caractéristiques pathologiques des kératinocytes psoriasiques in vitro. Des points de vue physiopathologique et pharmacologique, ce modèle devient pertinent pour une meilleure compréhension de désordres cutanés auto-immuns tel, le psoriasis.

No / In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

Yes / Interleukin-36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL-36 is now a recognised characteristic of psoriatic skin inflammation. IL-36 is known to induce inflammatory responses in dendritic cells, fibroblasts and epithelial cells. Although vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in skin inflammation, the effects of IL-36 on endothelial cells are unexplored. We here show that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated by IL-36γ stimulation and this is reversed by the presence of the endogenous IL-36 receptor antagonist. IL-36γ stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T cells following IL-36γ stimulation of endothelial cells. These results suggest a role for IL-36γ in the dermal vascular compartment and it is likely to enhance psoriatic skin inflammation by activating endothelial cells and promoting leukocyte recruitment.

Le psoriasis est une maladie inflammatoire de la peau pour laquelle aucun traitement curatif n’a vu le jour jusqu’à présent. L’étiologie étant complexe, la recherche dans ce domaine vise donc une meilleure compréhension de la pathologie. Pour ce faire, il faut mettre sur pied des modèles in vitro représentatifs de la pathologie, ce que nous faisons au LOEX. Ce projet porte sur la caractérisation par profilage génique de notre modèle afin d’en poursuivre l’optimisation éventuelle. Pour ce faire, nous avons produit différents substituts sains, lésionnels et non-lésionnels, puis nous en avons analysé le transcriptome. Dans un second temps, nous avons tenté de mimer la condition inflammatoire via l’addition de cytokines au sein des substituts lésionnels. Ces résultats démontrent d’une part la force du modèle existant, mais d’autre part, que la supplémentation en cytokines a des effets positifs sur le transcriptome, le rendant quasi identique à celui de peaux psoriasiques in vivo. / Psoriasis is a chronic inflammatory skin disease for which no cure has emerged. Research in this area aims to better understanding its complex etiology. Representative models of the pathology are needed and it is part of our expertise to develop psoriatic skin substitutes at LOEX. This project has focused on the characterization of our model by gene profiling in order to pursue its optimization. Different kinds of substitutes were produced and the transcriptome was analyzed. We also attempted to mimic the addition of immune cells via the addition of cytokines during lesional skin reconstruction. Cytokines chosen were identified as playing a key role in psoriasis. These results demonstrated on one hand, the strength of our original model and on the other hand, the positive impact on the transcriptome that cytokines supplementation can produce, making it almost identical to psoriatic skin in vivo.

Une adaptation de la méthode d’auto-assemblage développée au LOEX permet de produire des substituts cutanés bicouches ayant un phénotype psoriasique. Le premier objectif de ce travail était d’évaluer si une conservation par la congélation des substituts cutanés était envisageable afin d’avoir accès à ces derniers en tout temps pour effectuer des analyses physiochimiques sans délais. Les études réalisées sur des substituts sains montrent qu’elle ne l’est pas dans sa méthodologie actuelle puisqu’elle affecte la fonction barrière des substituts. Par ailleurs, en raison du rôle des lipides épidermiques dans la fonction barrière et de leur implication dans le psoriasis, une caractérisation de ces lipides a été effectuée par chromatographie en phase gazeuse. Les résultats obtenus montrent principalement une diminution de la proportion d’acide linoléique dans les substituts par rapport à la peau normale humaine. Ces résultats sont prometteurs en raison du rôle de cet acide et de ses métabolites dans l’inflammation. / Adaptation of the self-assembly method developed at LOEX allows us to produce bilayered skin substitutes with psoriatic phenotype. The first aim of this study was to evaluate if freezing of the skin substitutes is possible without affecting its integrity, in order to access the skin substitutes in anytime to perform physicochemical analysis without delay. Results, obtained with control skin substitutes produced via the standard described self-assembly method, showed that freezing clearly affected the skin barrier function of the skin substitutes. Moreover, because of their implication in skin barrier and in psoriasis pathology, epidermal skin lipids of control and psoriatic skin substitutes were characterized by gas chromatography. Results showed mainly a significant reduction of the linoleic acid proportion in skin substitutes compared to normal human skin. These results are promising because of the implication of linoleic acid and its metabolites in inflammation.

Le psoriasis est une maladie cutanée chronique et complexe à médiation immunitaire qui implique un large éventail de cellules épithéliales et immunitaires. Les mécanismes sous-jacents qui régissent les défauts épidermiques et le dysfonctionnement immunologique restent largement incompris. L'IL-17A, une cytokine de grande importance dans la pathogenèse du psoriasis, est en mesure d'activer les kératinocytes, lesquels sécrètent à leur tour diverses cytokines et chimiokines, conduisant à la chronicisation des lésions psoriasiques. Ces dernières années, l'émergence de nouveaux modèles plus sophistiqués a permis l'évolution de nos connaissances sur la pathogénèse du psoriasis. En raison des différences importantes entre l'immunité cutanée de l'humain et de l'animal, de nombreux effets secondaires imprévus et indésirables sont observés en clinique lors du développement de nouvelles thérapies contre le psoriasis. Il y a alors un réel besoin pour le développement de modèles précliniques humains adéquats pour l'étude du psoriasis. Le premier objectif de cette thèse était d'évaluer le profil d'expression génique du modèle de peau psoriasique de l'équipe du Dre Pouliot. De façon intéressante, bien que celui-ci ne soit produit qu'à partir de deux types cellulaires, soit les fibroblastes et les kératinocytes provenant de lésions cutanées de patients atteints de psoriasis, une quantité importante de gènes dont l'expression est dérégulée entre les conditions psoriasiques et leurs contrôles sains a pu être observée. Cependant, en raison de l'absence de la composante immunitaire dans le modèle psoriasique, certains gènes reconnus comme étant dérégulés dans la peau psoriasique native n'ont pas été révélés dans le modèle à l'étude. Le second objectif de cette thèse visait à optimiser le modèle de peau psoriasique enrichi en lymphocytes T. Les résultats issus de cette étude ont montré que le changement des méthodes de culture des lymphocytes T, notamment aux niveaux de leur isolation et activation, permet pour la première fois la production d'IL-17A dans les substituts psoriasiques. Cette étude a permis de présenter un nouveau modèle de peau psoriasique produit à partir de cellules cutanées psoriasiques, enrichi en lymphocytes T et présentant le microenvironnement pro-inflammatoire caractéristique du psoriasis, notamment par la présence d'IL-17A. Finalement, le dernier objectif de cette thèse visait à étudier de façon plus approfondie les mécanismes cellulaires et moléculaires impliqués dans le psoriasis à l'aide de ce modèle optimisé. Cette étude a mis de l'avant la dérégulation du produit du gène PTPRM dans les kératinocytes psoriasiques et sa contribution dans la pathogenèse du psoriasis via l'activation excessive de la signalisation ERK1/2. Globalement, nos travaux soutiennent l'importance des kératinocytes dans le développement des lésions psoriasiques. Les recherches présentées dans cette thèse ont également mené à la proposition d'un modèle sophistiqué de peau psoriasique enrichie en lymphocytes T qui peut s'avérer un outil intéressant pour le développement de nouvelles cibles thérapeutiques, ainsi que pour la médecine personnalisée. / Psoriasis is a chronic and complex immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms governing epidermal defects and immunological dysfunction remain largely misunderstood. IL-17A, a cytokine of great importance in the pathogenesis of psoriasis, can activate keratinocytes, which in turn secrete a variety of cytokines and chemokines, leading to the chronicization of psoriatic lesions. In recent years, the emergence of new and more sophisticated models has allowed the evolution of our knowledge on the pathogenesis of psoriasis. Because of the significant differences between human and animal skin immunity, many unexpected and undesirable side effects are observed in the clinic when developing new psoriasis therapies. There is therefore a real need for the development of adequate preclinical human models for the study of psoriasis. The first objective of this thesis was to evaluate the gene expression profile of Dr. Pouliot's psoriatic skin model. Interestingly, although the model is produced from only two cell types, fibroblasts and keratinocytes derived from skin lesions of psoriasis patients, a significant amount of deregulated gene expression between the psoriatic conditions and their healthy controls has been observed. However, due to the absence of the immune component in the psoriatic model, some genes known to be deregulated in native psoriatic skin were not revealed in this model. The second objective of this thesis was to optimize the T cell-enriched psoriatic skin model. The results of this study showed that the change in T cell culture methods, especially in their isolation and activation, allows for the first time the production of IL-17A in psoriatic substitutes. This study allowed the presentation of a new psoriatic skin model produced from psoriatic skin cells, enriched in T cells, and presenting the pro-inflammatory microenvironment characteristic of psoriasis, notably by the presence of IL-17A. Finally, the last objective of this thesis was to further investigate the cellular and molecular mechanisms involved in psoriasis using this optimized model. This study highlighted the deregulation of the PTPRM gene product in psoriatic keratinocytes and its contribution to the pathogenesis of psoriasis via excessive activation of ERK1/2 signaling. Overall, our work supports the importance of keratinocytes in the development of psoriatic lesions. The work presented in this thesis has also led to the proposal of a sophisticated T cell-enriched psoriatic skin model that may prove to be an interesting tool for the development of new therapeutic targets, as well as for personalized medicine.