Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by
autoantibody-mediated platelet destruction. To test the efficacy of novel sulfur compounds as
alternative treatments for ITP, we used a mouse model of passive immune thrombocytopenia
(PIT). Using this model, the platelet nadir could not be maintained, with platelet counts rising
after day 4, despite daily anti-platelet antibody administration. We examined reticulated platelet
counts by flow cytometry, and found increased thrombopoiesis in the bone marrow to be at least
partially responsible for this platelet rebound. Consequentially, two improved mouse models of
PIT were developed, where the platelet rebound is circumvented. The first model employs sublethal
total body gamma-irradiation in combination with daily antibody administration, while the
second model employs gradual escalation of the daily antibody dose. Finally, we show that none
of the tested candidate compounds show efficacy in elevating platelet counts in vivo, likely due
to their limited solubility.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/18786 |
| Date | 12 February 2010 |
| Creators | Katsman, Yulia |
| Contributors | Branch, Donald R. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0233 seconds