OXIDATIVE STRESS AND NUTRITION IN LUNG AND LIVER 
                            TRANSPLANT RECIPIENTS 
             
                                        
                                      by 
             
             
             
             
             
             
             
                                   Janet Madill  
             
             
             
             
             
                  A thesis submitted in conformity with the requirements  
                         for the degree of Doctor of Philosophy 
                             Institute of Medical Science 
                               University of Toronto 
                                        
                                        
                                        
                                        
                                        
                                        
                                        
                          © Copyright by Janet Madill (2010) 
             
                                                                   
                              ABSTRACT OF THESIS 
             
              Oxidative Stress and Nutrition in Lung and Liver Transplant 
                                   Recipients 
            Doctor of Philosophy, 2010, Janet Madill, Institute of Medical Science, 
                               University of Toronto 
                 
                Transplantation is an acceptable treatment for end)stage lung 
            and liver disease patients.  In lung transplantation, long)term survival 
            is limited due to Bronchiolitis Obliterans Syndrome (BOS) and in liver 
            transplantation, Hepatitis C Virus (HCV) disease recurrence 
            significantly impacts long)term survival.  Treatment options are limited 
            and often not successful.  It is therefore important to conduct research 
            on the factors contributing to the pathogenesis and disease severity of 
            BOS and HCV to improve our understanding of the mechanisms and 
            potentially reduce morbidity and mortality.  Several factors may play a 
            role.  The focus of this thesis is to assess the role of Oxidative Stress 
            (OxS) and nutrition on these patient populations.   
            BOS is a frequent complication of lung transplantation.  OxS may 
            contribute to its pathogenesis and induce further tissue injury and 
            inflammation.  OxS can be influenced by several factors including 
            nutrition.   The cross)sectional study showed that BOS lung recipients 
            have elevated markers of OxS in their Bronchoalveolar Lavage Fluid 
            (BALF) compared to those without BOS.  However, there was no 
            difference in nutritional factors potentially affecting OxS. 
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          HCV reinfection post transplant is universal, significantly increasing 
          morbidity and mortality.  OxS is involved in the pathogenesis of 
          chronic HCV but its role in HCV disease recurrence is unknown.  A first 
          study determined whether HCV liver recipients (HCV<) were more 
          oxidatively stressed when compared to controls or HCV non)transplant 
          patients.  A second study assessed OxS at six)and 12 months post 
          transplant and compared results between those with and without 
          recurrence. 
             The results showed that HCV)LT were more oxidatively stressed, 
          vitamin A intakes were significantly lower and plasma gamma) 
          tocopherol was significantly higher in HCV)LT.  Additionally, those with 
          recurrence were more oxidatively stressed at six)months (before 
          recurrence) and 12 months compared to those without recurrence.  No 
          differences were seen regarding nutrition parameters. 
          These results suggest that OxS is present in transplant recipients but 
          that nutritional factors do not play a significant role.  Other causes of 
          OxS likely play a more significant role such as the presence of 
          inflammation due to immunological reactions associated with BOS and 
          the generation of reactive oxygen species (ROS/RNS) seen in patients 
          with HCV disease. 
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            Acknowledgements 
                                        
            I would like to acknowledge all of the following people.  
             
            My kind and caring supervisor, Dr. Johane Allard who guided me 
            throughout this process, mentored me through some very difficult 
            times and challenged me to achieve my potential. 
             
            My son who has been a source of inspiration and has consistently 
            positively challenged me every step of the way. 
             
            My very dear best friend and PhD colleague, Colleen McMillan who has 
            been with me every step of the way.  Her constant emotional and 
            intellectual support is very much appreciated; I could never have done 
            this without her.  
             
            My very dear family, my mom, and to my wonderful ‘top of the line’ 
            late father who have believed in me, supported me and provided much 
            needed financial support. 
             
            My dear friends Maureen O’Dell and Marie Clare Ghattas who coached 
            counseled and mentored me as only dear friends can do.   
             
            My dear colleagues Lois Kacsandi and Carole Chatalalsingh who have 
            been there with me offering kindness, caring, support and leadership. 
             
            My very close lab colleagues, Ellie Aghdassi and Bianca Arendt, for 
            their helpful, insightful mentoring of my progress and for their 
            excellent comments regarding the content of these studies.   
             
            My wonderful supportive committee members Dr. Hillary Steinhart 
            Chung)Wai Chow, Dr. Les Lilly, Dr. Maha Guindi, as well as other 
            supportive staff Dr. George Therapondos, Dr. Gary Levy. 
             
            This research project would of course, not have been possible without 
            the enthusiasm and commitment of the lung and liver transplant 
            participants, a special thanks is extended to all of them. 
             
            A special thank you to Emma Tucker for her statistical support. 
                                        
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