الفهرس 
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Abstract
Abdominal adhesions are a common and serious complication in patients undergoing abdominal/pelvic surgery. They are the commonest cause of intestinal obstruction, secondary female infertility, ectopic gestation, and chronic abdominal and pelvic pain. the use of exogenous recombinant tPA in the reduction of adhesion is limited due to its short half life.
We tested the effect of endogenously secreted tPA produced by in vivo transfer of tPA gene. We showed that the short term overexpression (1 week) of tPA gene delivered by a replication defective adenoviral vector is sufficient for the period of time following peritoneal injury when the fibrinolytic activity is insufficient, known to be about 5-8 days. However, unmodified first generation adenoviral vectors might have some limitations in long term efficacy and safety for adhesion prevention gene therapy. The broad tropism of adenovirus allows the virus to infect many cell types and is responsible for virus dissemination to distant organs. In our study we used modified adenoviral vector (transductional and transcriptionaly modified) in order to develop an optimal adhesions ONnormal tissue OFF targeted adenoviral vector for effective and safe localized treatment of abdominal adhesions.
In our study, rats were subjected to peritoneal injury and assigned to two protocols; de novo adhesion formation protocol and recurrent adhesion formation protocol.
In de novo adhesion formation protocol, recombinant adenoviral vectors expressing lac z gene (Ad-CMV-lac z) was instilled after peritoneal injury in group 1 that serve as acontrol group whereas group 2 that received non-modified vector (Ad-CMV-tPA) and group 3that received modified vector (Ad-MSLN-sigma-tPA) serve as a treated groups. In recurrent adhesion formation protocol(groups 4,5,6) classified as denovo groups (groups1,2,3) respectively but recombinant adenoviral vectors were instilled after adhesiolysis. denovo groups were sacrificed after one week from the peritoneal injury.Recurrent groups were sacrificed after one week from the second peritoneal injury.The scores of 1st adhesion and the 2nd one were recorded. Expretion of vector in adhesion tissue was detected by RT-PCR analysis of h t-PA gene, adenovirus E4 detection by PCR analysis and detection of β-galactosidase activityby X-gal staining.