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EFFECTS OF COMBINED THERMAL AND RADIATION INJURY ON THE RENIN-ANGIOTENSIN SYSTEM
by
Sachin Suresh Jadhav
A Thesis Presented to the
FACULTY OF THE USC SCHOOL OF PHARMACY
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(PHARMACEUTICAL SCIENCES)
May 2010
Copyright 2010 Sachin Suresh Jadhav
Object Description
| Title | Effects of combined thermal and radiation injury on the renin-angiotensin system |
| Author | Jadhav, Sachin Suresh |
| Author email | ssjadhav@usc.edu; surflord@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pharmaceutical Sciences |
| School | School of Pharmacy |
| Date defended/completed | 2010-03-15 |
| Date submitted | 2010 |
| Restricted until | Unrestricted |
| Date published | 2010-04-27 |
| Advisor (committee chair) | Louie, Stan |
| Advisor (committee member) |
Shen, Wei-Chiang Rodgers, Kathleen |
| Abstract | The renin angiotensin system (RAS) plays an important role in wound repair. However, little is known pertaining to RAS expression in response to thermal and combination thermal/radiation injury. The combination of radiation exposure and radiation injury is a likely scenario in the event of a nuclear disaster, where the population found within the immediate blast radius will suffer from radiation exposure accompanied by thermal injuries.; It is well documented that radiation delays wound healing, it is thus hypothesized that the combination of thermal and radiation injuries will lead to a delay and decrease in RAS expression which will correlate with a delay in wound healing. The main purpose of this study was to evaluate the changes in the expression of genes for various components of RAS by RT-PCR in response to a thermal injury and compare to combined thermal plus radiation (CRBI). Confirmation that changes in AT1 gene expression lead to changes in protein expression was evaluated by IHC staining from the wound injury tissue.; The gene expression data show that in response to thermal injury by itself there is an initial increase in the expression of various components of RAS. In mice receiving the combined radiation and burn injury however, there is an initial decrease in gene expression. As the RAS has been shown to promote wound healing, this may contribute to the delay in wound response. The IHC data for AT1 expression, the receptor for which there is ample data for pro-proliferative activity, confirmed there is a delay and decrease in the number of fibroblasts, which are positively stained for AT1. These injury sites demonstrated a decrease in collagen deposition for animals receiving combined injury when compared to animals receiving the thermal injury only. When we studied the extent of wound healing by observing the keratinocytes infiltration into the wounded area, significant decrease in wound healing in the CRBI groups was observed as compared to the thermal injury only. All of this data, together with evidence from published studies that blockage of AT1 delays dermal healing, support the notion that delayed wound healing observed in subjects suffering from radiation exposure where temporal relationship with RAS expression is correlated.; Another aspect of radiation injury includes the level of cellular apoptosis. Ultraviolet radiation stimulates both apoptotic pathways. The number of apoptotic cells was determined by TUNEL staining in the wound site sections. Data suggest that mice receiving radiation alone do not show any marked increase in apoptosis. In mice treated with 100 cGy radiation + thermal injury we observed a similar pattern of apoptosis as that seen in the thermal injury only group. However, mice receiving 600 cGy radiation + thermal injury reveal a delay and an increase in the number of apoptotic cells as compared to the thermal or radiation injury only. |
| Keyword | radiation; angiotensin; wound healing; gene expression; immunohistochemistry; apoptosis |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2962 |
| Rights | Jadhav, Sachin Suresh |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Jadhav-3637 |
| Archival file | uscthesesreloadpub_Volume29/etd-Jadhav-3637.pdf |
Description
| Title | Page 1 |
| Full text | EFFECTS OF COMBINED THERMAL AND RADIATION INJURY ON THE RENIN-ANGIOTENSIN SYSTEM by Sachin Suresh Jadhav A Thesis Presented to the FACULTY OF THE USC SCHOOL OF PHARMACY UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (PHARMACEUTICAL SCIENCES) May 2010 Copyright 2010 Sachin Suresh Jadhav |
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