ABSTRACT OF INVITED LECTURES AND ORAL PRESENTATION

FP7-07CAN BOVINE LACTOFERRIN-CONTAININGPRODUCTS PROTECT CHILDREN FROMNOROVIRUS OUTBREAK?Hiroyuki Moriuchi , Masanori Egashira, MasakoMoriuchiDepartment of Pediatrics, Nagasaki University Hospital, Nagasaki, Japan;Department of Molecular Microbiology and Immunology, NagasakiUniversity Graduate School of Biomedical Sciences, Nagasaki, Japan.BACKGROUND: Norovirus is an important cause ofacute gastroenteritis worldwide, and its outbreaks amonginstitutionalized adults or children have accumulated in thepast years. Nevertheless, no specific preventive ortherapeutic agent has been available yet. Lactoferrin (LF),a milk-derived glycoprotein with a number of biologicalactivities, has recently been reported to have anti-noroviruseffect in vitro. We have recently reported that daily intakeof bovine LF (bLF) reduced the severity of rotavirusgastroenteritis in children; however, its effect on norovirusgastroenteritis remains unknown.OBJECTIVE: To investigate if bLF could protect healthychildren against norovirus gastroenteritis.DESIGN/METHODS: Healthy children (less than 5 yearsold) attending day-care centers (DCC) were randomlydivided into two groups: L group assigned to take 400 mgof bLF daily for 16 weeks and N group assigned not totake LF-containing products. Guardians were asked torecord clinical symptoms and signs on a daily basis duringthe study period. Feces were collected from all childrenwith acute gastroenteritis, and tested for rotavirus withimmunochromatographic assays (ICA) and norovirus withICA and real-time RT-PCR.RESULTS: A total of 91 children (46 in L group and 45 inN group) were analyzed for the incidence of gastroenteritiscaused by rotavirus or norovirus. Two in L group and nonein N group developed mild rotavirus gastroenteritis duringthe study period. Based on ICA, 2 (4.3%) in L group and 7(15.6%) in N group developed norovirus gastroenteritis (p< 0.01). Norovirus real-time RT-PCR revealed 2 patients(4.3%) in L group and 9 (20%) in N group, consisting of 5in GI genotype and 6 in GII genotype.CONCLUSIONS: Daily intake of bLF products reducedthe incidence of norovirus gastroenteritis in healthychildren attending DCC. Taken together with our previousstudy, LF appears to protect healthy children from viralgastroenteritis. Real-time RT-PCR had better sensitivitythan ICA, and was capable of genotyping.[Keywords] norovirus, gastroenteritis, lactoferrin, day care centerFP8-01HERG GENE MUTATIONS ORPOLYMORPHISMS IN PATIENTS WITHREPAIRED TETRALOGY OF FALLOT: APOTENTIAL RISK FOR VENTRICULARARRHYTHMIASShuenn-Nan Chiu, M.D 1 , Ming-Tai Lin, M.D 1 , Mei-HwanWu, M.D, PhD, FHRS 1 , Chien-Chih Chang, M.D 1 ,Hue-Wen Hsu, M.D 1 , Jou-Kou Wang, M.D, PhD 1 ,Chun-An Chen, M.D 1 , Ching-Tsuen Shen, M.D, PhD 2 ,Olivier Thériault, PhD 3 , Mohamed Chahine, PhD 31 Department of Pediatrics, National Taiwan University Hospital and College ofMedicine, National Taiwan University, Taipei, Taiwan; 2 Department ofPediatrics, Cathay General Hospital, Taipei, Taiwan; 3 Hôpital Laval, ResearchCentre, Sainte-Foy, Quebec, Canada, G1V 4G5, and Department of Medicine,Université Laval, Quebec City, Quebec, Canada, G1K 7P4BACKGROUND: hERG gene mutations/polymorphisms areassociated with congenital and acquired long QT syndrome.However, the effects of these changes on the repolarizationabnormality, secondary to complete right bundle branch block,in repaired Tetralogy of Fallot (TOF) patients are stillunknown. This study sought to define the role of hERG genemutations in ventricular arrhythmias in these patients.METHODS AND RESULTS: We analyzed the mutations orsingle nucleotide polymorphisms (SNPs) in all exons of thehERG gene in 83 patients with repaired TOF and completedhemodynamic and electrocardiographic data. Additionally, invitro biophysical characterization of mutant alleles wasperformed using whole-cell voltage clamp after expression inXenopus oocytes. Two novel mutations (p.M645R and p.R92C,one in each) and one non-synonymous SNP (p.K897T, threepatients) were found in five (6.0%) patients. Life-threateningevents occurred in six patients and were more common in thosewith genetic variants (2/5 vs. 4/78, p=0.040). The patient withp.M645R mutation experienced cardiac arrest two years aftercardiac repair. One patient with p.K897T SNP died suddenly35 years after cardiac repair. Expression of the p.M645Rmutant allele alone in Xenopus oocytes resulted in no currentgeneration while co-expression of the mutant and wild-typealleles showed a net decrease in I Kr .CONCLUSION: In patients with TOF, the coexisting hERGmutations and non-synonymous SNP might have additiveeffects on the repolarization abnormality from right bundlebranch block after cardiac repair and may potentially increasethe risks of ventricular arrhythmias in repaired TOF patients.[Keywords]hERG gene, mutation, Tetralogy of Fallot, ventriculararrhythmia, complete right bundle branch block84