Graduate StudentAbstract # 35Hayley Spencer 1,2 , Rachel Wade 2 , Fanny Chu 1 , Hélène Côté 2 <strong>and</strong> David Walker 1,21Providence Heart + Lung Institute at St. Paul’s Hospital, 2 Department of <strong>Pathology</strong> <strong>and</strong><strong>Laboratory</strong> <strong>Medicine</strong>, <strong>University</strong> of British Columbia, Vancouver, BC, CanadaHayley Spencerliver ultrastructural damage in hepatitis C virus <strong>and</strong>HIV co-infected individualsBackround/ObjectivesIn the developed world, end-stage liver disease is the leading cause of death for patients infected with HumanImmunodeficiency Virus (HIV). Among HIV-infected individuals, the Hepatitis C Virus (HCV) coinfection rate inVancouver is estimated to be 50% (82% among intravenous drug users), in contrast to 33% in the developed world.Livers of coinfected patients suffer repeated damage via many avenues, with HCV chronicity resulting in acceleratedliver fibrosis <strong>and</strong> often hepatocellular carcinoma. Life-long management of HIV infection by HAART (Highly-ActiveAnti-Retroviral Therapy) includes the use of nucleoside-analog reverse transcriptase inhibitors (NRTIs), some of whichare known to exert toxic effects on the mitochondria <strong>and</strong> decrease mitochondrial DNA (mtDNA). Mitochondrialtoxicity can also result from anti-viral combination therapy for HCV; ribavirin (an NRTI) is used in conjunction withpegylated interferon to treat HCV infection. Treatment duration <strong>and</strong> efficacy vary depending on HCV genotype <strong>and</strong>other factors. To investigate the direct effects of ribavirin <strong>and</strong> pegylated interferon combination therapy in individualson <strong>and</strong> off-HAART, we will employ morphometric <strong>and</strong> qualitative ultrastructural analyses to characterize liver biopsyspecimens obtained before <strong>and</strong> after anti-HCV combination therapy. To do so, hepatocyte transmission electronmicroscope (TEM) images <strong>and</strong> mtDNA content will be examined before <strong>and</strong> after treatment..MethodsTwo ultrasound-guided 10mm/18 gauge needle liver biopsies are obtained from fasting coinfected patients underlocal anaesthetic before <strong>and</strong> after HCV combination therapy. The first liver biopsy is examined by a single, blindedpathologist <strong>and</strong> scored for fibrosis <strong>and</strong> inflammation. The second biopsy is divided into 4 aliquots for analysisof DNA, for TEM imaging, <strong>and</strong> for future analysis of RNA <strong>and</strong> protein. mtDNA content will be analysed byquantitative PCR <strong>and</strong> expressed as a ratio of mtDNA to nuclear DNA, with a correction for the presence ofbinucleate hepatocytes. The TEM quarter of the biopsy is cut into 1mm3 pieces, <strong>and</strong> immediately fixed in 2.5%glutaraldehyde, sodium cacodylate buffered solution. After washes in buffer, specimens are post-fixed with osmium<strong>and</strong> potassium ferrocyanide, dehydrated, infiltrated, <strong>and</strong> embedded in epoxy resin (Epon). Thick sections (500 nm)are cut <strong>and</strong> stained with Toluidine Blue O for reference. Thin sections (60 nm) are cut <strong>and</strong> mounted on Formvarcoated grids before staining with 2% uranyl acetate <strong>and</strong> Reynold’s lead citrate. Sections are cut on a Leica EM UC6ultramicrotome, <strong>and</strong> viewed in a FEI Tecnai 12 TEM at 80kV. Images are acquired with a Gatan BioScan 792camera <strong>and</strong> associated Gatan software. Image-Pro software will be employed for morphometry, with a blinded singleexaminer. .ResultsWith careful analysis of morphometric data, we expect to observe ultrastructural changes after anti-HCV combinationtherapy in hepatocytes such as hypertrophy, changes in mitochondrial volume fractions, <strong>and</strong> evidence of alteredmetabolism such as changes in glycogen accumulation <strong>and</strong> lipid volume fractions. We also anticipate the possibilityof alterations in other organelles such as peroxisomes, lysosomes <strong>and</strong> the endoplasmic reticulum. At the tissue level,there is a possibility of damage manifested as a change in overall biopsy score as described by the pathologist, <strong>and</strong> ameasurable decrease in the mtDNA content of the hepatocytes.46 2 0 1 0 * P o s t e r P r e s e n t a t i o n s
Graduate StudentTuhina Imam 1 , Hugo Soudeyns 4 , Norm<strong>and</strong> Lapointe 4 , Marissa Jitratkosol 1 ,Beheroze Sattha 1 , Johanne Samson 4 , Tessa Chaworth-Musters 3 , John Forbes 2,3 ,Deborah Money 1,2 <strong>and</strong> Hélène Côté* 1,21Univ of British Columbia, Vancouver, Canada, 2 Women`s Health Research Institute,Vancouver, Canada, 3 Children`s <strong>and</strong> Women`s Health Centre of BC, Vancouver, BC, Canada,4Centre de Recherche du CHU Ste-Justine, Montreal, QC, CanadaAbstract # 36Tuhina Imamperipheral blood telomere length in infants <strong>and</strong> theirHIV-infected mothers treated with antiretroviraltherapy during pregnancyBackround/ObjectivesZidovudine (ZDV) is routinely used in antiretroviral therapy (ART) during HIV pregnancy, to prevent verticaltransmission. ZDV inhibits telomerase, the enzyme responsible for telomere elongation. We hypothesized that bloodaverage telomere length (ATL) would be shorter in ART-exposed mothers <strong>and</strong> their infants compared to those whowere untreated.MethodsThis retrospective cohort spanning 1990-2000 included HIV-infected pregnant women who were untreated, ortreated with mono-, dual- or triple-therapy during their pregnancy. Maternal <strong>and</strong> infant dried blood spots (DBS) werecollected at the last visit before delivery <strong>and</strong> at 0-6 weeks, respectively. DBS relative ATL was measured by qPCR.ATL were compared between treated <strong>and</strong> untreated mothers <strong>and</strong> infants using ANCOVA. Covariates included:maternal age, gestational age, smoking <strong>and</strong> recreational drug use. In linear regression analyses, additional possiblepredictors considered included, ART pre-pregnancy, duration of ART in pregnancy, maternal CD4 <strong>and</strong> pVL (plasmaviral load) at last pre-delivery visit (when available) <strong>and</strong> age of infant at time of sample (infant ATL only).ResultsInfant ATL measured at a median [IQR] 1 [1-4] days of age were longer than maternal ATL (p
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- Page 11 and 12: ResidentClinical SciencesArwa Al-Ri
- Page 13 and 14: ResidentTitus Wong 1 , Marc Romney,
- Page 17 and 18: ResidentD. Turbin 1 , D. Gao 2 , J.
- Page 19 and 20: ResidentDavid F Schaeffer 1 , Eric
- Page 21 and 22: ResidentMajid Zolein 1 , Daniel T.
- Page 23 and 24: Graduate StudentAshish K. Marwaha 1
- Page 25 and 26: Graduate StudentAmanda Vanden Hoek
- Page 27 and 28: Graduate StudentXin Ye 1 , Mary Zha
- Page 29: Graduate StudentLisa S. Ang 1 , Sar
- Page 32 and 33: Graduate StudentAbstract # 22Brian
- Page 36 and 37: OtherAbstract # 25Crystal Leung, Li
- Page 38 and 39: OtherAbstract # 27Lise Matzke 1 , W
- Page 40 and 41: Graduate StudentAbstract # 29Varun
- Page 42 and 43: Graduate StudentAbstract # 31Maite
- Page 44 and 45: Post-doctoral FellowAbstract # 33Ra
- Page 48: Post-doctoral FellowAbstract # 37Es
- Page 51 and 52: ResidentAhmad Al-Sarraf MD 1, 2 , G
- Page 53 and 54: OtherRebecca Towle 1 , Danielle Mac
- Page 55 and 56: Graduate StudentPaul R. Hiebert 1,2
- Page 57 and 58: Graduate StudentV. Montoya 1 , J. G
- Page 59 and 60: OtherWalter Martz and Henry Kalicia
- Page 61 and 62: OtherKatelyn J. Janzen 1 , Elizabet
- Page 63 and 64: Graduate StudentJasmine L. Hamilton
- Page 65 and 66: Graduate StudentIan M. Wilson 1 , K
- Page 67 and 68: Graduate StudentKelsie L. Thu 1,3 ,
- Page 69 and 70: OtherLiat Apel-Sarid 1 , Doug Cochr
- Page 71 and 72: Graduate StudentJennifer R. Choo 1,
- Page 73 and 74: Graduate StudentEdwin S. Gershom 1
- Page 75 and 76: OtherYing Qiao 1, 2 , Chansonette H
- Page 77 and 78: Graduate StudentLeslie YM Chin 1,4
- Page 79 and 80: Graduate StudentBillie Velapatiño
- Page 81 and 82: Graduate StudentSophie Stukas 1 , S
- Page 83 and 84: Graduate StudentKyluik DL and Scott
- Page 85 and 86: Post-doctoral FellowJoel Montane 1
- Page 87 and 88: IndexAAbozina A. 45Abraham T. 55All
- Page 89: Ye X. 27, 82Yee S. 31Yoshida E. 12Y