Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Thèse--Méd.--Reims, 1973. N°: N° 19. / Bibliogr. ff. I-XI.

Universität Leipzig, Dissertation 77 Seiten, 78 Literaturangaben, 9 Abbildungen, 5 Tabellen Die Psoriasis vulgaris ist eine chronisch-entzündliche Hautkrankheit, bei der unter anderem neutrophile Granulozyten (PMNC) beteiligt sind. Bei der Einwanderung dieser Zellen spielen Adhäsionsmoleküle wie beispielsweise das humane Thy-1 auf aktivierten Endothelzellen eine wichtige Rolle. Interessanterweise variiert die Stärke der Adhäsion neutrophiler Granulozyten an Thy-1: Bereits nach einer zweitägigen Standardtherapie der Psoriasis ist eine Reduktion der Thy-1-Adhäsion der PMNC feststellbar. Dieser Befund sollte nun an einer größeren Patientengruppe überprüft werden. Zuvor musste geklärt werden, ob es eine einfachere und schnellere Methode zur Bestimmung der Adhäsion neutrophiler Granulozyten an Thy-1 als das bisherige Standardverfahren, einem Adhäsionsassay an Thy-1 - transfizierte CHO – Zellen, gibt. Daher wurde als alternative Methode ein Adhäsionsassay von PMNC an immobilisierten, rekombinantem, humanem Thy-1 (rThy-1) untersucht. Jedoch stellte das Alternativverfahren keine Verbesserung im Vergleich zum Standardverfahren dar. Im Folgenden wurde daher die Standardmethode verwendet, um in einer Phase IV Studie die Thy-1-Adhäsion unter Therapie mit Efalizumab bei 18 Patienten mit einer mittelschweren bis schweren Psoriasis vulgaris vom Plaque-Typ (PASI >12) zu untersuchen. Die Ergebnisse zeigten, dass die Thy-1-Adhäsion von Respondern (Patienten mit Psoriasis, die auf Efalizumab mit einer PASI-Reduktion über 50% nach 12wöchiger Therapie reagieren) bereits vor Beginn der Therapie im Vergleich zu der Thy-1-Adhäsion bei Non-Respondern (PASI-Reduktion unter 50%) erhöht war. Zudem zeigten die neutrophilen Granulozyten von Respondern im Gegensatz zu Non-Respondern bereits in den ersten beiden Wochen nach Beginn der Behandlung eine signifikant abnehmende Adhäsion an Thy-1. Somit könnte die Bestimmung der Adhäsion neutrophiler Granulozyten an Thy-1 möglicherweise sowohl vor Beginn als auch während einer Therapie mit Efalizumab ein prognostischer Marker zur Diskriminierung von Respondern und Non-Respondern sein.

M.Tech.

Proefschrift--Utrecht. / Vita. Summary in English. Includes bibliography.

Syfte och frågeställningar Syftet med studien är att ta reda på i hur hög grad svenska psoriatiker håller sig fysiskt aktiva. Syftet konkretiseras i två frågeställningar: Följer de svenska psoriatikerna de allmänna rekommendationerna för fysisk aktivitet? Har de blivit informerade av sjukvården om vikten av fysisk aktivitet för att förebygga de följdsjukdomar som är kopplade till psoriasis? Metod En tvärsnittsundersökning i form av en webbenkät gjordes bland svenska psoriatiker. Svenska psoriasisförbundet hänvisade till enkäten genom sin Facebookgrupp. 125 personer med psoriasis besvarade enkäten. IPAQ-S valdes som undersökningsinstrument för den fysiska aktiviteten. Resultat Resultatet visade att 25 procent av de som svarade på enkäten inte nådde upp till en nivå av fysisk aktivitet motsvarande de allmänna rekommendationerna för fysisk aktivitet. Resultatet visade också att de svarande hade ett högt BMI (29 ± 8). Få personer hade fått information om den ökande risken för hjärt- och kärlsjukdomar i samband med psoriasis av sin hudläkare(9,6 procent) eller annan hälsopersonal (6,4 procent). Förhållandevis få personer (18,8 procent) hade fått rekommendationer om fysisk aktivitet av någon hälsopersonal och endast 3,4 procent hade fått det av sin hudläkare. Slutsats Resultaten av undersökningen är inte generaliserbara pga. urvalet. Men undersökningen visar att det kan vara så att informationen om de ökade riskerna för hjärt- och kärlsjukdomar samt rekommendationer för fysisk aktivitet är bristfällig till psoriatiker, trots rekommendationer att läkare bör informera psoriasispatienter att bedriva fysisk aktivitet. / Aim The purpose of the study is to find out how much the Swedish psoriasis patients are physically active. The aim embodied in two questions: Are swedish people with psoriasis following the general recommendations for the physical activity? Have they been informed by health care staff of the importance of physical activity for the prevention of comorbidities linked to psoriasis? Method A cross sectional survey in the form of a web questionnaire was made on people with psoriasis in Sweden. The Swedish Psoriasis Association referred to the survey through their Facebook group. 125 people with psoriasis responded to the questionnaire. IPAQ-S was chosen as the survey instrument for physical activity. Results The results showed that 25 percent of those responding to the survey did not reach a level of physical activity equivalent to the general recommendations for physical activity. The results also showed that the respondents had a high BMI (29 ± 8). Few people had received information about the increased risks of cardiovascular disease associated with psoriasis by their dermatologist (9.6 percent) or other health care professionals (6.4 percent). Relatively few people (18.8 percent) had received recommendations on physical activity from health care personnel, and only 3.4 percent had received it from their dermatologist. Conclusion The survey results are not generalizable due to the selection. But it may be that information about the increased risks of cardiovascular disease and recommendations for physical activity is insufficient to psoriasis patients, despite recommendations that doctors should inform their psoriasis patients to engage in physical activity.

No description available.

No description available.

No description available.

A psoríase (Ps) é uma doença inflamatória crônica-imunomediada da pele, caracterizada por proliferação acentuada e diferenciação anormal de queratinócitos e aumento do infiltrado de células inflamatórias na derme. S100A9 é um alarmina que é produzida por queratinócitos e células mielóides em condições inflamatórias. No entanto, o papel desta molécula no desenvolvimento e manutenção da resposta inflamatória da Ps permanece desconhecida. Nesso objeitvo foi investigar o papel de S100A9 no desenvolvimento da psoríase. Análises de bioinformática de um banco de dados disponível on-line contendo valores de expressão de gênica de humanos mostrou que a expressão de S100A9 está aumentada pele lesionada de pacientes com Ps. Esses dados foram confirmados por imunofluorescência e Western blot onde foi observado um aumento na expressão de S100A9 na pele lesionada de pacientes com Ps, em comparação com amostras de pele não lesionada desses mesmo pacientes. Estes níveis de S100A9 foram positivamente correlacionados com a expressão de queratina-17, um marcador de ativação de queratinócitos. Para investigar o papel do S100A9 no desenvolvimento de Ps, autilizamos o modelo de Ps induzido por aplicação tópica de imiquimode (IMQ) nas costas de de camundongos WT, S100A9 - / - ou camundonos previamente tratados com paquinimod (10mg / kg, vo ), um quelante de S100A9. A exposição ao IMQ induziu o aumento da expresão gênica de S100a9 e proteica de forma rápida e dependente do tempo na pele e nos linfonodos drenantes da pele, e esse aumento permaneceu elevado até o final do experimento (6º dia). Notavelmente, a inflamação, e espessura da pele foram significativamente reduzidas em camundongos tratados com PAQ ou camundongos S100A9 -/- em comparação com camundongos WT. Os parâmetros histológicos confirmam a redução da espessura da epiderme, mostrada por seções histológicas coradas com HE. Para determinar quais células produtoras de S100A9 contribuem para o desenvolvimento de Ps, realizamos uma quimera e mostramos que ambos os queratinócitos e células mieloides são importantes para a produção de s100a9 e contribuem para o desenvolvimento da psoríase. No entanto os queratinócitos parecem ser mais importantes no aumento da espessua e na lesão da pele. Além disso, a expressão de Il23, na pele de animais S100A9 -/- ou tratados com PAQ foi reduzida, o que poderia explicar a redução das linfócitos T gamma-delta IL-17 nos linfonodos desses mesmos camundongos. Nosso trabalho mostrou que o alarmina S100A9 desempenha um papel importante no desenvolvimento da psoríase. Assim, S100A9 poderia ser uma estratégia futura para o tratamento farmacológico da psoríase. Além disso essa proteína poderia ser usada como marcador da atividade da doença / Psoriasis (Ps) is an immune-mediated chronic inflammatory skin disease, characterized by accentuated proliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells in the dermis. S100A9 is an alarmin that is produced by keratinocytes and myeloid cells in inflammatory conditions. However, the role of this molecule in the development and maintenance of the inflammatory response in Ps remains not well understood. Herein, we investigated the role of S100A9 in the development of psoriasis. Bioinformatical analysis of an online database containing human gene expression information showed that the s100a9 is overexpressed in lesional skin from Ps patients. These data were confirmed by immunofluorescence and western blot that showed an overexpression of s100a9 in the lesional skin from Ps patients compared with paired samples of nonlesional psoriatic skin. These levels of s100a9 were positively correlated with the expression of keratin-17, a keratinocyte activation marker. To investigate the role of S100A9 in the development of Ps, psoriasis-like skin inflammation was induced by topical application of imiquimod (IMQ) on the back skin of S100A9-deficient mice (S100A9-/-) or paquinimod (10mg/kg, v.o) pretreated mice. IMQ exposure induced s100a9 mRNA and S100A9 protein expression in a rapid and time-dependent manner in the skin and lymph node of mice and remained elevated until the end of the experiment (6th day). Notably, inflammation, assessed by epidermal thickness measurement and H&E-stained histological sections, was significantly reduced in S100A9-/- or paquinimod treated-mice compared with wild-type (WT) control mice. To determine which S100A9- producing cell contributes to the Ps development we performed a chimera and showed that both keratinocytes and myeloid cells are important for the production of s100a9 and contribute to the development of psoriasis. However keratinocytes seems to be most important to development of lesion skin. Moreover, the expression of IL-23, in the skin, was reduced, which might explain the reduction of IL-17-producing gamma-delta T cells in the lymph nodes of S100A9-/- or paquinimod-treated mice. We showed that the alarmin S100a9 plays an important role in the development of psoriasis. Thus, targeting S100A9 could be a future strategy for pharmacological treatment of psoriasis and this protein can be used as a marker of disease activity.