Check of Antiviral Activity of Nanocomposites with Active Check of Antiviral Activity of Drugs Based on Nanocomposites, Which Contained Oligonucleotides for Direct Splitting Viral Genome of Influenza
- 作者：Dmitriy Pletnev ; Aleksei Evdokimov ; Evgeniy Belanov ; Ernst Malygin ; Sergey Balachnin ; Olga Serova ; Viktor Zinoviev ; Valentina Zarytova ; Asya Levina ; Marina Repkova ; Zinfer Ismagilov ; Nadegda Shikina
- 关键词：Astrocytes ; Urotensin II ; UT ; GABAAR ; cAMP ; Polyphosphoinositide
- 刊名：Antiviral Research
- 出版年：2008
- 期刊代码：7_01663542
- 类别：imm
- 出版时间：May 2008
- 卷：78
- 期：2
- 页码：A46
- 文件大小：69 K
摘要
Current pancreatic islet transplantation protocols achieve remarkable short-term success, but long-term insulin independence remains elusive. Hypoxic and inflammatory insults cause substantial early posttransplant graft loss while allo/autoimmunity and immunosuppressive drug toxicity threaten long-term graft mass and function. Exendin-4 (Ex4) is a GLP-1 receptor agonist that promotes β-cell proliferation, survival, and differentiation. To determine whether Ex-4 displays potential as a graft-supportive agent, we transplanted 500 murine islets under the kidney capsule of syngeneic or allogeneic streptozocin-treated recipient mice and immediately initiated daily treatment with vehicle or Ex4. Graft β-cell proliferation, death, and vascularity were assessed at 1, 3, and 10 days after syngeneic islet transplantation. For allogeneic recipients, blood glucose and body weight were assessed until glycemic deterioration. Ex-4 did not promote graft β-cell proliferation, reduce β-cell death, or enhance graft vascularity over the first 10 days after syngeneic islet transplantation. A trend toward prolongation of posttransplant euglycemia was observed with Ex4 treatment in nonimmune-suppressed allograft recipients, but its use in this setting was associated with frequent, severe hypoglycemia over the first 2 posttransplant days. Our findings do not support a beneficial effect of Ex-4 on islet grafts during the critical early posttransplant period, further, they demonstrate a significant hypoglycemic potential of Ex-4 in the first days after islet transplantation in mice. Optimal application of GLP-1 receptor agonists for long-term proliferative and survival benefits in transplantation may require earlier intervention prior to and/or during islet isolation for peri-transplant cytoprotection and administration beyond the period of engraftment.