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Study On Therapeutic Effect Of Paclitaxel Solutions In Treatment With Psoriasis-like Model Of Guinea Pig

Posted on:2004-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y N WangFull Text:PDF
GTID:2144360092490768Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Psoriasis is one of the most prevalent chronic inflammatory disorders of the skin (which affects more than 0.123% of people in China and 0.2% in Europe), but the precise pathogenesis of psoriasis remains unclear today, resulting in the difficulty of its control and treatment. By 1980s, psoriasis had been thought by the vast majority of researchers as a process of abnormal regulation of keratinocyte growth, and the accompanied inflammation was regarded as a secondary feature. However, in the past decades, with the rapid developments in cellular immunology and basic pathology, it was gradually found that abnormal immune procedures and subsequent inflammatory interactions played a major role in psoriasis. Up to now the disease was defmited as 'an autoimmune disease of skin mediated by T cells'. Therefore, novel interventions for psoriasis have focused not only on inhibiting the over-proliferation of keratinocyts, but also on contradicting the abnormalimmune steps. At the same time, the research on developments of immune-based therapies for psoriasis has dominated this field.Paclitaxel has been clinically used as an anti-tumor agent. Approved by FDA in early 1990s for treatment of malignant tumors such as ovary cancer and breast cancer, the microtubule stabilizer has been studied extensively for its unique effects on cells. It is generally accepted that paclitaxel can arrest the cell cycle in various cells and inhibit their proliferation by altering microtubule assembly, but it isn't pointed out until recently that paclitaxel could also affect a series of important immunopathogenic functions in cells (including migration, chemotaxis, adhesiveness and intracellular transportation). Therefore, it is hypothesized that paclitaxel might have a therapeutic effect on the immunopathogenic steps in psoriasis. To our knowledge, it is the first time that the therapeutic effect of paclitaxel on psoriasis-like animal model has been studied despite of previous reports about preventive and protective effect of paclitaxel on other animal models of autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. ObjectiveTo observe the effect of local usage of paclitaxel solution on skin of psoriasis-like animal model and to get message whether it is possible to treat psoriasis with paclitaxel, psoriasis-like model on guinea pigs' ears was established. Paclitaxel DMSO solution with a concentration of 200ug/ml and 500ug/ml, as well as a positive control agent (momestasone cream) was delivered on the models. Then the effects of paclitaxel DMSO solution on models were evaluated according to the Baker score, the amount of infiltrated inflammatory cells and the pathological changes of major organs (including heart, liver, lung and kidney). Methods5% Propranolol ointment was applied on Guinea pigs' ears three times per day for 3 weeks to establish a psoriasis-like model of guinea pig, and these animals were randomly devided into 9 groups. Group 1, raised for 3 weeks for normal control; group 2, psoriasis-like models group; group 3, after establishement of psoriasis-like models, observed for 2 weeks; group 4, 40% dimethyl sulfoxide (DMSO) solution was delivered on the models three times per day for 2 weeks; group 5, momestasone cream was delivered on the models three times per day for 1 week; group 6, paclitaxel DMSO solution with a concentration of 200ug/ml was delivered on the models three times per day for 1 week; group 7, paclitaxel DMSO solution with a concentration of 200ug/ml was delivered on the models three times per day for 2 weeks; group 8, paclitaxel DMSO solution with a concentration of 500ug/ml was delivered on the models three times per day for 1 week; group 9, paclitaxel DMSO solution with a concentration of 500ug/ml was delivered on the models three times per day for 2 weeks. Then the animals were sacrificed with their ears and major organs (including heart, liver, lung and kidney) fixed into 4% formaldehyde solution. After hematoxylin and eosin (HE) staining, the pathological changes and the amo...
Keywords/Search Tags:psoriasis, paclitaxel, animal-model
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