College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
SCHEDULE
09:30 AM
WELCOME
DR KAREN DOYLE, VICE DEAN OF GRADUATE STUDIES, COLLEGE OF MEDICINE, NURSING & HEALTH SCIENCES
09:35 AM
OPENING OF MEETING
PROF TIM O’BRIEN, DEAN OF COLLEGE OF MEDICINE, NURSING & HEALTH SCIENCES
SESSION 1
CHAIR: DR SEAN DINNEEN, HEAD OF SCHOOL OF MEDICINE
09:45 – 10:00
CONOR HENNESSY
The effect of epigenetic modifications on TLR 3 expression
10:00– 10:15
SHAHD HORIE
Activation of mesenchymal stromal cells enhances the protective effects of their secretome on the pulmonary epithelium
10:15 – 10:30
JOANNE KENNEY
The role of the arcuate fasciculus in verbal learning performance in psychosis
10:30 – 11:00
INVITED SPEAKER: DR MOLLY BYRNE, HEALTH BEHAVIOUR CHANGE RESEARCH GROUP
Changing human behaviour for health: How to be more effective
11:00 - 11:25
MORNING COFFEE BREAK
ARTS MILLENNIUM BUILDING FOYER
SESSION 2
CHAIR: DR ADELINE COONEY, HEAD OF SCHOOL OF NURSING
11:25 - 11:40
LORRAINE BURKE
The context and circumstances of early sexual initiation: a mixed methods investigation
11:40 - 11:55
MARY CALLAGHAN
An exploration of bullying among post-primary school children in Ireland
11:55 - 12:10
SAMIRA DHAMAPURKAR
Continuing improvement after a long period of impaired consciousness
12:10 – 12:25
AOIFE GAVIN
Changing family structure and life satisfaction among children in Ireland: analysing trends between 1998 and 2010
12:25 - 12:40
HELEN GREALISH
Assessing how research evidence is used in public health policy documents: a policy content analysis
12:40 – 12:55
NURUL KODRIATI
The current status of smoking and drinking alcohol among Indonesian men: Descriptive results of Masculinity Survey 2012
12:55 - 14:15
LUNCH & POSTER SESSION
ARTS MILLENNIUM BUILDING FOYER
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
SESSION 3
CHAIR: DR THOMAS RITTER, VICE DEAN RESEARCH, COLLEGE OF MEDICINE, NURSING & HEALTH SCIENCES
14:15 - 14:30
MARTIN MADILL
Investigation of Amyotrophic Lateral Sclerosis disease mechanisms using patient derived fibroblasts and induced pluripotent
stem cells
14:30 - 14:45
KATE MCDONNELL-DOWLING
Prenatal or postnatal exposure to methamphetamine impairs neonatal development and behaviour in rat offspring
14:45 - 15:00
SERIKA NAICKER
Peripheral blood monocyte profiles and P2X7 expression in chronic kidney disease (CDK) and end-stage renal disease (ESRD)
15:00 - 15:15
KILLIAN O’BRIEN
Clinical application of circulating microRNAs as biomarkers is hindered by lack of standardised protocols
15:15 - 15:30
GRACE O’MALLEY
The effect of NF-KB on tumour-stromal interactions in colorectal cancer
15:30 - 15:50
AFTERNOON COFFEE BREAK
ARTS MILLENNIUM BUILDING FOYER
SESSION 4
CHAIR: DR KAREN DOYLE, VICE DEAN GRADUATE STUDIES, COLLEGE OF MEDICINE, NURSING & HEALTH SCIENCES
15:50 – 16:05
STEFANI O’DONOGHUE
Disrupted anatomical integration and rich club connectivity in Euthymic Bipolar Disorder
16:05 – 16:20
LINDSAY SULLIVAN
An evaluation of a concussion education programme for youth GAA athletes and coaches
16:20 – 16:35
SHARON CONWAY
Gestational weight gain and sleep hygiene: results from a European pilot clinical trial of lifestyle intervention
16:35 PRIZE GIVING & CLOSE OF MEETING
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ORAL PRESENTATIONS
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
The Effect of epigenetic modifications on TLR 3 expression
Author(s) and
Affiliation(s)
Conor Hennessy Declan Mckernan
1
1
1
Discipline of pharmacology and therapeutics. School of medicine
ABSTRACT
Toll-like receptors (TLRs) are a family of receptors that recognise pathogen associated molecular
patterns (PAMPS) which are structurally conserved molecules present on bacteria and viruses. TLR3 is
a double stranded RNA sensor and is thought to play an important role in viral sensing and the
subsequent immune response. However the factors that regulate the expression of TLR3 are not well
known. Epigenetic changes are changes in the expression of genes without a change in nucleotide
sequence, which is in contrast with traditional genetics which focuses on changes induced by
alterations in nucleotide makeup. We posit that epigenetic changes can alter the expression of TLR3
and the signalling cascade initiated by TLR3. Epigenetic changes can be induced by altering states of
methylation and acetylation which alter gene expression by manipulating chromatin structure and
function, acting to increase or decrease expression of genes as a result. In this study we used two cell
lines, HCT-116 human epithelial cells and THP-1 human monocytes. The cells were treated with
Histone deacetylase complex (HDAC) inhibitors and DNA methyltransefrease (DNMT) inhibitors
followed by a stimulation with the synthetic analogue for dsRNA, POLY I:C. The purpose of this was to
examine the effect of inhibition of methtylation and histone deacetylation on TLR3s response to viral
stimulation. Inhibition of HDACS and DNMTs resulted in a large decrease in TLR3 expression,
furthermore increases in TLR3 expression due to stimulation with POLY I:C were completely abolished
with inhibition of HDACs and DNMTs. Changes in the levels of TLR expression also resulted in changes
in the levels of cytokines produced, notably significantly altered levels of IL-6, TNF-α and IFN-β when
POLY I:C treated cells were pre-treated with the inhibitors of HDACs and DNMTs. These results
present a compelling argument for epigenetic regulation of TLR3.
References
1. Takeda, K., Akira, S., 2005. Toll-like receptors in innate immunity. Int. Immunol. 17(1); 1-14.
2. Li, E., 2002. Chromatin modification and epigenetic reprogramming in mammalian development.
Nat. Rev. Genet. 3(9): 662-673.
3. Livak KJ & Schmittgen TD., 2001. Analysis of relative gene expression data using real-time
quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25(4):402-8..
Acknowledgements
College of science, NUI Galway
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
ACTIVATION OF MESENCHYMAL STROMAL CELLS ENHANCES THE PROTECTIVE EFFECTS OF THEIR
SECRETOME ON THE PULMONARY EPITHELIUM
1, 2
1, 2
1,3
Shahd Horie, MSC , Dr. Daniel O’Toole, PhD , Prof. John G. Laffey, MD, FCARCSI .
Author(s) and
Affiliation(s)
1
Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway;
2
3
Regenerative Medicine Institute, National University of Ireland, Galway, Ireland; and Department of
Anaesthesia, Keenan Research Institute, St Michaels Hospital, and University of Toronto, Canada.
Rationale: Human Mesenchymal Stromal cells (hMSCs) have been shown to be therapeutic in several
ABSTRACT
models of Acute Lung Injury (ALI) and are entering clinical testing for ARDS. The immuno-modulatory
and regenerative properties of hMSCs appear in part, to be due to their release of soluble factors. We
wished to determine whether pre-activating hMSCs could further enhance the protective effects of
their secretome on the pulmonary epithelium.
Methods: hMSCs were pre-activated for 24 hours in the presence of different cytokines including IFNγ and IFN-β. Cells were then re-fed with serum free media and the conditioned medium (CM) was
harvested 24 hours later. Alveolar type II A549 cells incorporating an NF-κB luciferase reporter
construct were grown to mono-layers and subjected to oxidative stress, inflammatory cytokines,
scratch wounding and mechanical cyclic stretch injury. Cell viability, NF-κB induction, secreted
inflammatory cytokines and wound healing were assessed.
Results: CM from hMSCs attenuated IL-1β induced NF-κB induction in the pulmonary epithelial monolayer when compared to control (MEM-α) media. Furthermore CM from hMSCs pre-activated with
IFN-γ and IFN-β was more effective in inhibiting NF-κB induction when compared to CM from naive
hMSCs. Activated hMSC CM also alleviated oxidative stress and cyclic mechanical stretch injury to a
greater extent than that of the CM from naïve hMSCs, however, the promotion of wound healing was
comparable.
Conclusions: Pre-activating hMSCs enhances the therapeutic benefits of their secretome in vitro, a
finding that warrants further investigation in relevant pre-clinical models. Additional clarification is
also required regarding the mechanisms involved.
Acknowledgements
This study was supported by funding from the HRB, ERC and SFI.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
The role of the arcuate fasciculus in verbal learning performance in psychosis.
1,2
2
1
1,3
1
Joanne Kenney , Genevieve McPhilemy , Heike Anderson-Schmidt , Cathy Scanlon , Shane McInerney ,
4
5
1
Alexander Leemans , Ben Jeurissen , Colm McDonald , Dara M. Cannon
Author(s) and
Affiliation(s)
ABSTRACT
1
1
2
2
Clinical Neuroimaging Laboratory, Departments of Psychiatry & Anatomy, School of Medicine, College of
3
Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland, Department of
Psychiatry and Psychotherapy, Section of Psychiatric Genetics, University Medical Centre Goettingen, Georg4
5
August-University, Germany , Image Sciences Institute, University Medical Center Utrecht, The Netherlands,
Vision Lab, University of Antwerp, Belgium.
Cognitive deficits are prevalent in schizophrenia, in particular verbal learning ability has been noted
as being one of the most pronounced deficits compared to healthy controls (Aas et al, 2014).
Previously, we identified performance on verbal learning to be more impaired than other cognitive
tests up to four years following an initial psychotic episode. In order to investigate if any
abnormalities in the arcuate fasciculus (AF) contribute to this impairment in verbal learning in
psychosis, we isolated this white matter tract and investigated its relationship with verbal learning
performance.
Twenty-two individuals who experienced a first psychotic episode (FEP) and 27 healthy controls (HC)
underwent cognitive testing and diffusion-weighted MR scanning at first-presentation and four-years
later. Cross-sectional analysis was conducted on data from the follow-up time point.
The long, anterior and posterior segments of the arcuate fasciculus were isolated using a region of
interest (ROI) approach following recursively calibrated CSD based tractography (Explore DTI). Using
measures of tract volume, lateralisation of the tract was calculated for each segment and correlation
analysis conducted with a measure of verbal learning, the Hopkins Verbal Learning Test.
Verbal learning scores correlated with lateralisation of the posterior segment of the AF in healthy
controls (r=0.46, p=0.018), with a stronger association evident following removal of left-handed
individuals (r=0.57, p=0.004). A concurrent association was not found in the FEP group (right-hand
only; r=0.13, p=0.66). Verbal learning did not correlate with the long segment (HC: r=0.02 p=0.94;
FEP: r=-0.21 p=0.48) or anterior segment (HC: r=-0.04 p=0.87; FEP: r=0.05 p=0.86) of the AF.
More pronounced left lateralisation of the arcuate fasciculus was associated with better performance
in verbal learning in healthy controls only. In the psychosis group, the absence of this left
lateralisation pattern in the role of verbal learning may explain the deficits evident in their
performance.
References
1.Aas, M., Dazzan, P., Mondelli, V., Melle, I., Murray, R.M., Pariante, C.M., 2014. A systematic review
of cognitive function in first-episode psychosis, including a discussion on childhood trauma, stress,
and inflammation. Front. Psychiatry, 2014, 4, 182.
2. Catani, M., Jones, D. K. & Ffytche, D. H. Perisylvian language networks of the human brain. Annals
of Neurology, 2005, 57, 8-16.
Acknowledgements
We would like to thanks the participants, the radiographers and Radiology Department at UCHG. This work was
supported by a Health Research Award from the Health Research Board.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
THE CONTEXT AND CIRCUMSTANCES OF EARLY SEXUAL INITIATION: A MIXED METHODS
INVESTIGATION
Author(s) and
Affiliation(s)
Lorraine Burke , S. Nic Gabhainn and C. Kelly
ABSTRACT
Early sexual initiation has been associated with adverse sexual health outcomes at the time of first
sexual intercourse and also later in life. Research indicates that adolescent sexual initiation patterns
vary across countries internationally, however, limited data exists in Ireland. Our research has shown
that 21.2% of Irish adolescents have had sex before the legal age of 17. Of the adolescents (15-18
years) who reported being sexually active, 22.8% of boys and 13.4% of girls reported sexual initiation
before age 14. A number of socio-demographic and lifestyle factors were also found to predict sexual
intercourse before the age of 14 years (1). While these provide an insight into possible factors
influencing sexual initiation little is known about the specific correlates of early sexual initiation.
This study aims to investigate the context and circumstances surrounding first sexual intercourse
occurring on or before the age of 15 years. Phase one of the methodology will include quantitative
analysis of sexual behaviour data collected through the 2014 Health Behaviour in School-aged
Children Ireland study. Standardised questions on sexual behaviour will be supplemented by
specifically developed questions on the context and experience of sexual initiation (e.g., alcohol/drug
consumption, sexual partner, contraception use). The second phase will explore the views of
adolescents aged 15-17 through a series of focus groups discussing findings arising from phase one
and participants’ views on the issues as they arise. The study will provide an up-to-date
understanding of the factors influencing Irish adolescent sexual initiation and could potentially
identify risk factors of early sexual initiation that may be amenable to intervention. It will provide a
foundation for the development of health promotion strategies and policies aimed at reducing sexual
health outcomes such as Sexually Transmitted Infection (STI) acquisition, teenage pregnancy and
negative health, well-being, educational and economic outcomes.
1
1
1
1
Discipline of Health Promotion, School of Health Sciences, NUI Galway
References
1. Young, H., Burke, L., Nic Gabhainn, S. Sexual behaviour, initiation and contraception among
adolescents in Ireland: Findings from the Health Behaviour in School-aged Children (HBSC) Ireland
study. 2013.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
AN EXPLORATION OF BULLYING AMONG POST-PRIMARY SCHOOL CHILDREN IN IRELAND
Author(s) and
Affiliation(s)
Mary Callaghan1, C. Kelly1 and M. Molcho1
1
Discipline of Health Promotion NUI Galway
ABSTRACT
Bullying is a major cause of concern among parents, teachers and children as it has substantial effects
1,2
on children’s lives . It is defined as repeated negative behaviour with the intent to cause harm,
3
within the context of an unequal power relationship . The negative effects of traditional bullying are
well established, however there is limited research on cyber bullying. Traditional bullying victims are
4
2
more likely to experience poor health and poorer psychological outcomes , and bullies are more
5
likely to report involvement in substance use such as drinking and taking drugs . The aim of this study
was to explore the associations of bullying victimisation with self-reported health and life satisfaction,
and to examine whether involvement in risk behaviours contributes to these health outcomes. Data
were collected on involvement in traditional and cyber bullying, self-reported health, life satisfaction
and risk behaviours from students aged 15 to 18 years old using classroom based paper surveys. In
total, 318 students from 8 post-primary schools took part in the study. We found that children who
reported being victims of bullying were more likely to report poor health, low life satisfaction and
engaging in risky behaviours. Although not statistically significant, cyber victimisation was positively
associated with increased reporting of poor health and low life satisfaction. Traditional bullying was
the most common type of bullying reported among school children in this study, and overall, seems
to have a stronger association with poor health. However, a sizable proportion of children reported
being victims of cyber bullying or of both cyber and traditional bullying. Understanding the effects of
all types of bullying is important to improve the health outcomes of children and prevent bullying
among school children.
References
1.
Bannink, R., Broeren, S., van de Looij-Jansen, P.M., de Waart, F.G., Raat, H. Cyber
and traditional bullying victimization as a risk factor for mental health problems and
suicidal ideation in adolescents. PLoS One, 2014.
2.
Menesini, E., Modena, M., Tani, F. Bullying victimization in adolescence: concurrent and
stable roles and psychological health symptoms. J. Gene. Psychol., 2009; 115-134.
Olweus, D. Bullying at school: what we know and what can we do. Blackwell publishers,
Oxford. 1993.
Due, P., Holstein, B.E., Lynch, J., Diderichsen, F., Nic Gabhainn, S., Scheidt, P., Currie, C.; The
Health Behaviour in School-Aged Children Bullying Working Group. Bullying and symptoms
among school-aged children: international comparative cross sectional study in 28 countries.
Eur. J. Public Health, 2005; 128-132.
Radliff, K.M., Wheaton, J.E., Robinson, K., Morris, J. Illuminating the relationship between
bullying and substance use among middle and high school youth. Addict. Behav., 2012; 569572.
3.
4.
5.
Acknowledgement
s
This study was supported by funding from the Department of Health. We would also like to
acknowledge the children and parents who consented and participated, the management
authorities, principals and teachers who helped us to collect the data.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
CONTINUING IMPROVEMENT AFTER A LONG PERIOD OF IMPAIRED CONSCIOUSNESS.
1,3
Author(s) and
Affiliation(s)
ABSTRACT
1, 2,
3
1
Samira Dhamapurkar , Barbara Wilson , Agnes Shiel , Anita Rose and Gerhard Florschutz
1
Raphael Medical Centre, Tonbridge, Kent, UK
2
Oliver Zangwill Centre, Ely, UK
3
University of Galway, Ireland
1
Background and aims: Severity of brain injury is determined by the depth and duration of coma.
Most patients who recover from coma open their eyes by four weeks post injury. They are then no
longer in coma. They may have recovered full consciousness or they may still have reduced
awareness/a disorder of consciousness. Only about 9 per cent of patients who remain with a disorder
of consciousness after several months show some recovery. There is a paucity of evidence on the
type of recovery shown by such patients. The aim of this study is to show the gradual improvement of
a man who sustained a TBI through an assault and who remained with a disorder of consciousness for
nineteen months before emerging from the minimally conscious state (MCS).
Method: The patient was assessed repeatedly through his two year stay at a rehabilitation hospital
with the Wessex Head Injury Matrix, The JFK coma recovery scale, and the Sensory Modality
Assessment Rehabilitation Techniques. He also received intensive inpatient multi-disciplinary
rehabilitation.
Results: The patient remained in a vegetative state for nearly 14 months before progressing to the
MCS where he remained for a further five months. He then emerged from the MCS. Over the next
eight months he continued to improve both cognitively and physically to such an extent that he can
now function with minimal assistance.
Conclusions: Even after long periods of impaired consciousness, it is possible for patients to show
meaningful improvement if they receive appropriate rehabilitation and assessment.
References
Giacino, J.T., Kalmar, K. and Whyte, J. (2004). The JFK Coma Recovery Scale-Revised: measurement
characteristics and diagnostic utility. Arch Phys Med Rehabil. 85, 2020-9.
Gill-Thwaites, H. and Munday, R. (2004). The Sensory Modality Assessment and Rehabilitation Technique
(SMART): a valid and reliable assessment for vegetative state and minimally conscious state patients. Brain
Injury. 18, 1255-69.
Shiel, A., Wilson, B. and McLellan, D.L. (2000). Wessex Head Injury Matrix (WHIM) Manual. London: Harcourt
Assessment.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
CHANGING FAMILY STRUCTURE AND LIFE SATISFACTION AMONG CHILDREN IN IRELAND:
ANALYSING TRENDS BETWEEN 1998 and 2010.
Author(s) and
Affiliation(s)
Aoife Gavin , C. Kelly , S. Nic Gabhainn and M. Molcho
1
1
1
1
1
School of Health Sciences, NUI Galway
ABSTRACT
Young people whose parents are either separated or divorced form an increasing proportion of
society. Previous studies have highlighted the importance of family structure to health and wellbeing outcomes among young people. Life satisfaction is an indicator of well-being as well as future
well-being. The present study will examine the association between family structure, parental
communication and life satisfaction among young people in Ireland. Changes in the associations over
time will be explored between 1998 and 2010.
The Health Behaviour in School-aged Children (HBSC) survey is a WHO (Europe) collaborative survey.
HBSC Ireland has been collecting data every four years from representative samples of young people
since 1998. This paper employs binary logistic regression models where life satisfaction acts as the
dependent variable and family structure and parental communication predictor variables. Within the
models, the variable ‘HBSC survey year’ is treated as a predictor using the repeat contrast function
allowing comment on statistically significant changes over time. Age, gender and social class were
controlled for in all models. Analyses were conducted using SPSS v.20.0.
Overall, there has been a significant decrease in the proportion of young people who report living
with both parents (91.5% in 1998 vs. 78.4% in 2010). There has been a significant increase in the
proportion of young people reporting high life satisfaction between 2002 and 2010. Across all logistic
regression models, family structure remains a strong predictor of life satisfaction as does poor
parental communication.
This presentation will discuss the findings with a focus on social
inequalities against the backdrop of the rise and fall of the Celtic Tiger.
References
Acknowledgements
1. Gavin, A., Molcho, M., Kelly, C. & Nic Gabhainn, S. (2013). The HBSC Ireland Trends Report 1998-2010: Child
Health Behaviours, Outcomes and Contexts. Dublin: Department of Health.
2. Levin, KA., Dallago, L., and Currie, C. (2012). The association between adolescent life satisfaction, family
structure, family affluence, gender differences in parent-child communication. Social Indicators Research,
106:287-305.
This study was supported by funding from Department of Health
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
ASSESSING HOW RESEACH EVIDENCE IS USED IN PUBLIC HEALTH POLICY DOCUMENTS: A POLICY
CONTENT ANALYSIS
Author(s) and
Affiliation(s)
Helen Grealish and Saoirse Nic Gabhainn
1,2
Health Promotion Research Centre: National University of Ireland, Galway
ABSTRACT
Background: This study is exploring how research evidence impacts on health and public policymaking in the area of alcohol and drugs from 2001 - 2012. “Research impact” is defined as how
1
research activities contribute to policy-making in order to improve population health outcomes . This
retrospective case study is using a triangulation of methods: document analyses of policy documents
and key informant interviews with researchers and policy makers working in the area of alcohol and
drugs. Findings from phase one of the studies – quantitative content analyses of health policy
documents is presented in this paper.
Methods: Documents selected for inclusion in the study were accessed from the Department of
Health and Children, and the Drugs and Alcohol websites between July and October 2013. The
2
“Framework” method was used in the analyses of the policy documents . This is particularly suited to
research that has a pre-designed sample and a priori set of questions. The documents were examined
to determine the; i) type of information referenced on the policy document, ii) the purpose of
reference to information in the documents and, iii) the frequency of reference to academic research.
Results: The most frequently referenced type of information on drug policy documents was external
legislation/reports (n=41), followed by studies which have been commissioned and carried out by
government agencies (n=37) and international research (n=21). International research was the most
frequently cited information on the alcohol reports (n=46), followed by international reports (n=37)
and Irish academic research (n=30). Justification for the policy was the main purpose of reference to
all types of information.
Conclusion: Although it is apparent that authors take a broad and considered approach to the
research that has been conducted in this policy area, specific references to academic research appear
to be regularly omitted from published documents.
References
1. Banzi, Rita, et al. "Conceptual frameworks and empirical approaches used to assess the impact of health
research: an overview of reviews." Health Res Policy Syst 9.1 (2011): 26.
2. Ritchie, Jane, and Liz Spencer. "Qualitative data analysis for applied policy research." The qualitative
researcher’s companion (2002): 305-329.
Acknowledgements
This study was supported by funding from***
1
2
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Author(s) and
Affiliation(s)
ABSTRACT
THE CURRENT STATUS OF SMOKING AND DRINKING ALCOHOL AMONG INDONESIAN MEN
DESCRIPTIVE RESULTS OF MASCULINITY SURVEY 2012
Nurul Kodriati, L.Pursell
Discipline of Health Promotion
Introduction:
A gender perspective of health behaviour acknowledges that to be male or female influences how a
person might behave concerning their health risks. Gender constructs have portrayed men as ‘being
macho’ and the backbone of the social environment[1]. For men this leads to an internal conflict
between the ideal man and the actual man. As a consequence of such internalisation, males may
partake in health damaging behaviours such as smoking and drinking alcohol[2]. In Indonesia,
smoking is regarded as a symbol of masculinity, while women, in general, have benefited from a
cultural resistance to their smoking[3]. This presentation describes the prevalence of smoking and
drinking alcohol Indonesia.
Methods:
Data was derived from a cross-sectional quantitative study that formed part the UN multi country
study of men and masculinity. The study comprised 10,000 men aged 18 - 49 years old who had been
randomly selected for interview in 6 Asian and Pacific countries (including Indonesia) during 20102012. This preliminary descriptive analysis of data from that study focuses on Indonesia, where the
study was conducted in three different areas: Jakarta, Purworejo and Jayapura.
Results:
The response rate was 85.9% of who (49.8%) had secondary school level of education (66.7%), were
married and (82.8%) were employed. Responses to indicators of health risk status related to smoking
and drinking alcohol showed that 12.5% reported problems with drinking alcohol with the highest
percentage in Papua (25.9%) and 70.8% reported being daily smokers with a mean number of
cigarettes per day/person of 9.9 ±7.5 and a mean starting age of 16.1 ±5.3 years old.
Conclusion:
Smoking and drinking alcohol are public health issues in Indonesia. Smoking is prevalent in all three
cities meanwhile, drinking alcohol is more prominent in Jayapura than in the other two cities.
Key words: smoking, drinking alcohol, masculinism
References
Acknowledgements
1.Hasyim, N., Kurniawan, A.P., and. Hayati, E.N. Menjadi Laki-laki: Pandangan Laki-laki Jawa Tentang
Maskulinitas dan Kekerasan Dalam Rumah Tangga. Rifka Annisa Press. Yogyakarta. 2007.
2.Gigele, I., Rozentale, G., and Skrule, J. The gender gap in life expectancy. SVA, Public Health Agency:
Riga.2007.
3.Ng, N., Chronic Disease Risk Factors in A Transitional Country:The Case of Rural Indonesia. Umeå: Umeå
University.2006.
This study was supported by funding from UNWomen Indonesia and guidance from Partners for Prevention (P4P)
based in Bangkok. The study was done under provision of Rifka Annisa, a NGO and women crisis center based in
Yogyakarta, Indonesia. This abstract is part of PhD program funded by LPDP (Indonesia Endowment Fund for
Education)
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Investigation of Amyotrophic Lateral Sclerosis disease mechanisms using patient derived fibroblasts
and induced pluripotent stem cells.
Author(s) and
Affiliation(s)
Martin Madill , P. McLoughlin , K. McDonagh , A. Vajda , O. Hardiman , and S. Shen
1
Regenerative Medicine Institute, National University of Ireland, Galway.
2
Trinity Biomedical Sciences Institute, Trinity College Dublin.
ABSTRACT
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterised by the
progressive loss of both upper and lower motor neurons. Death typically occurs within 3-5 years of
onset. With a prevalence of 5.4 per 100,000 population it registers as the third most common
1
neurodegenerative disease.
1
1
1
2
2
1
Mutations in many genes have been identified as causative in ALS, the most common of which occur
in the SOD1, TDP-43, FUS, and the recently identified C9ORF72 genes. However, despite much
research, the mechanisms by which these mutations induce motor neuron death remain elusive.
Further, known mutations only account for 10% of all ALS cases, with 90% having no known genetic
cause.
Herein we aimed to investigate the potential of ALS patient derived fibroblasts and induced
pluripotent stem cells (iPSCs) to model disease mechanisms. Our data suggest a likely role for SOD1,
FUS and C9ORF72 in autophagy, a pathway involved in the degradation and recycling of long-lived
and misfolded proteins. Additionally, we demonstrate that patients display impaired initiation of
autophagy as well as perturbed autophagic flux. Treatment with Rapamycin, a suggested therapeutic
for ALS, ameliorates some aspects of impaired autophagy. Patients also exhibit increased
susceptibility to apoptotic induction via oxidative stress, possibly due to impaired autophagic
mechanisms.
These results indicate that patient derived cells may recapitulate disease mechanisms in vitro and
may represent a valuable tool in drug screening.
References
Acknowledgements
1.
Chiò A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA.. Global
epidemiology of amyotrophic lateral sclerosis: a systematic review of the published
literature. Neuroepidemiology. 2013; 41:118-30.
This study was supported by funding from the National University of Ireland, Galway. Grants RSU002 and
RSF1296.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
PRENATAL OR POSTNATAL EXPOSURE TO METHAMPHETAMINE IMPAIRS NEONATAL
DEVELOPMENT AND BEHAVIOUR IN RAT OFFSPRING
Author(s) and
Affiliation(s)
1,2
Kate McDonnell-Dowling
and J.P. Kelly
1,2
1
Discipline of Pharmacology and Therapeutics, College of Medicine, NUI, Galway, Ireland
2
Galway Neuroscience Centre, National Centre for Biomedical Engineering Science, NUI, Galway, Ireland
In recent years, there has been a growing concern about methamphetamine (MA) use during
ABSTRACT
pregnancy and/or lactation in humans. However, there are limited preclinical studies investigating
MA’s potential harm on offspring development at these different exposure times. The aim of this
study was to determine if prenatal or postnatal MA exposure at a pharmacological dose affects
neurodevelopment and behaviour in the rat offspring. Pregnant Sprague-Dawley dams (n=8-10
dams/group) received MA (3.75mg/kg) or control (distilled water) daily via oral gavage either from
gestation day 7-21 or postnatal day 1-21. A range of well-recognised neurodevelopment parameters
were examined in the offspring. Data were analysed using Repeated-Measures ANOVA and Two-way
ANOVA or Friedman’s ANOVA and Kruskal-Wallis with relevant post-hoc tests. The level of
significance was p<0.05. Maternal weight gain was significantly reduced in the prenatal and postnatal
MA groups which was accompanied by reduced food intake. Pup mortality was increased in the
prenatal MA group (stillborn) and in the postnatal MA group (in the neonatal period). Both MA
treatment groups also showed significant impairments in developmental parameters including
somatic development (e.g. weight gain, pinna unfolding) and behavioural development (e.g. negative
geotaxis, surface righting, forelimb grip).
This study demonstrates that MA, at a pharmacological dose, can have a profound effect on neonatal
outcome when administered prenatally or postnatally. If extrapolated to the clinical scenario, this will
give cause for concern regarding the risks associated with this drug of abuse on neonatal
neurodevelopment.
Acknowledgements
This study was supported by funding from a PhD fellowship awarded by the College of Medicine, NUI, Galway,
Ireland.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
PERIPHERAL BLOOD MONOCYTE PROFILES AND P2X7 EXPRESSION IN CHRONIC KIDNEY DISEASE
(CKD) AND END-STAGE RENAL DISEASE (ESRD)
1
Author(s) and
Affiliation(s)
ABSTRACT
1
3
1
2
4
4
4,
4
Naicker S. , Logue S. , Cotter, D. , O’Malley G. , Hanley S. , Gleeson, J. , O’Connor, S. , Reddan, D. O’Regan, J. ,
4
4
4
4
3
1
1,4
Cormican, S. , Lappin, D. , Giblin, L. , Kieran, N. , Tormey V. , Ceredig R. and Griffin M.D.
1
2
Regenerative Medicine Institute (REMEDI), School of Medicine and Flow Cytometry Core Facility, National
University Ireland, Galway, Ireland.
3
4
Immunology and Nephrology Services, Saolta University Hospital Group, Galway, Ireland.
Introduction:
Chronic kidney disease (CKD) is associated with systemic inflammation which is linked to increased
morbidity and mortality and is exacerbated in patients requiring haemodialysis (HD) for end-stage
renal disease (ESRD). Altered circulating monocyte repertoire has been described as a component of
CKD-associated chronic inflammation and may directly contribute to accelerated cardiovascular
disease and immune dysfunction. We examined blood monocyte repertoires of individual peripheral
blood monocyte subsets in a cohort of patients with CKD of varying stages of severity, including ESRD.
We also evaluated monocyte subset expression of the inflammasome-activating ligand-gated cation
channel P2X7 in a cohort of patients with CKD or ESRD.
Methods:
CKD severity was divided into 5 stages based on estimated glomerular filtration rate (eGFR). PBMCs
from healthy adults (CTRL, n=25), patients with CKD stages 1-5 (n=100) or with ESRD prior to and after
HD (n=32) were analyzed by 8-colour flow cytometry to quantify monocyte subsets
++
++
+
+
++
[Classical(CD14 CD16 ), Intermediate(CD14 CD16 ), Non-classical(CD14 CD16 )] and their surface
expression of P2X7.
Results:
Total monocyte number progressively increased compared to CTRL from CKD stage 1-5 and in ESRD.
Subset analysis demonstrated that intermediate monocytes were most significantly increased in a
CKD stage-dependent manner. ESRD patients additionally demonstrated increased number of nonclassical monocytes which decreased markedly following HD. Surface expression of P2X7 was readily
detected on the surface of all monocytes subsets in CRTL, CKD Stages 1-5 and ESRD but was most
highly expressed by non-classical and a subpopulation of intermediate monocytes. Compared to
CTRL, all stages of CKD were associated with higher monocyte expression of P2X7 but, in ESRD, this
was further increased on non-classical monocytes following HD.
Conclusions:
Consistent with prior reports, we observed a stage-dependent increase in circulating monocytes in
CKD which disproportionately affected the intermediate subset. ESRD was uniquely associated with
non-classical monocytosis and this subset exhibited marked modulation following HD including
further upregulation of the inflammasome-activating receptor P2X7.
References
Acknowledgements
Heine G.H., Ortiz A., Massy Z.A., Lindholm B., Wiecek A., Martínez-Castelao A., Covic A., Goldsmith D.,
Süleymanlar G., London G.M., Parati G., Sicari R., Zoccali C & Fliser D. Monocyte Subpopulations and
Cardiovascular risk in Chronic Kidney Disease . Nat Rev Nephrol 8(6) 362-9. 2012
This study was supported by funding from Molecular Medicine Ireland, PRTLI and College of Medicine, Nursing
and Health Science
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Clinical application of circulating microRNAs as biomarkers is hindered by lack of standardised
protocols
Author(s) and
Affiliation(s)
Killian O’Brien, E. Ramphul, M. Kerin and R. Dwyer
Discipline of Surgery, NUIG, Galway City, Galway, Ireland
ABSTRACT
Introduction: MicroRNAs are short non-coding strands of RNA with potential as circulating biomarkers
of breast cancer. However, variations are seen throughout this field in starting material (whole
blood(WB),serum and plasma) methods of extraction, and endogenous controls(ECs) employed. This
has resulted in the publication of contradictory findings. This study aimed to investigate the variations
in approaches used.
Method: WB, serum and plasma samples from the same individuals were collected(n=90). WB was
collected in either 1)PAXgene™ tubes with subsequent PreAnalytix kit(Qiagen) RNA extraction or
2)EDTA tubes with subsequent Trizol® BD RNA extraction. Plasma and sera were collected, followed
by microRNA extraction using the miRCURY™ kit(Exiqon). RQ-PCR was carried out targeting miR-16,
miR-138, miR-504 and miR-379 for all samples.
Results: In 47 studies analysing circulating microRNAs in breast cancer, all three source materials
were implemented with 16 different methods of extraction and >20 different ECs employed. Analysis
of the same targets by different groups yielded conflicting results. The WB samples collected in
PAXgene™/Peanalytix(Qiagen) were found to have relatively stable microRNA expression with a miR16 range of 14-16Ct. In contrast EDTA/Trizol BD samples ranged from 14-30Ct for the same microRNA
target. WB, serum and plasma originating from the same individual was analysed (n=90). miR-138 and
miR-504 were detected in all WB samples, but undetectable in 32% and 38% of serum and plasma
samples respectively.
Conclusion: The starting material and method of processing chosen has a significant impact on
microRNAs detected and their profile of expression. Standardisation of protocols is critical to support
reliable identification of clinically relevant biomarkers.
Acknowledgements
This study was supported by funding from the Irish Cancer Society initiative BREAST PREDICT
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
THE EFFECT OF NF-ΚB ON TUMOUR-STROMAL INTERACTIONS IN COLORECTAL CANCER
Author(s) and
Affiliation(s)
G O’MALLEY1,2, P LOHAN2, S RANI2, K LYNCH2, S NAICKER2, G SHAW2, T RITTER2, LJ EGAN1,AE RYAN1,2
1
2
ABSTRACT
DEPT. OF PHARMACOLOGY AND THERAPEUTICS, NUI GALWAY
REGENERATIVE MEDICINE INSTITUTE (REMEDI), NUI GALWAY
Introduction
The tumour microenvironment (TME) is composed of many cell types including endothelial cells,
stromal cells and immune components, and influences tumour growth, metastasis and resistance to
therapy. It has recently been shown that mesenchymal stromal cells (MSCs) are recruited to the TME
and acquire a distinct, tumour-promoting phenotype in vivo. We aimed to elucidate the molecular
regulation of the induced immunosuppressive and tumour-promoting phenotype of tumourassociated MSCs, and specifically the effect of tumour cell NF-κB activity on this process.
Materials/Methods
NF-κB-deficient CT26 colon tumour cell lines were established by over-expression of an IκB-α superrepressor plasmid (CT26/IκB-α SR) with transfection of an empty vector as control (CT26/EV). MSCs
were treated with 60% conditioned medium from these cells (TCM) for 72hrs and subsequently cocultured with syngeneic t-cells. Migration was assessed using a transwell-based assay.
Results
MSC migration toward tumour cells was significantly inhibited in the absence of NF-κB in tumour
cells. After 72hr exposure to TCM, MSCs displayed an enhanced immunosuppressive capacity, which
was further increased when the tumour cells had been pre-treated with TNF-α. This enhanced
immunosuppression was dependent on NF-κB. Flow cytometry showed that TCM induced PD-L1
expression on MSCs, and the addition of a PD-1 blocking antibody reversed the enhanced
immunosuppression by the conditioned MSCs.
Conclusion
This data demonstrates that targeting the unregulated PD-1/PD-L1 signalling pathway in colorectal
cancer may be key to breaking the cycle of immunosuppression and immune evasion established by
stromal cells in the tumour microenvironment, thus providing an opportunity for more efficacious
cancer immunotherapy.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Disrupted Anatomical Integration and Rich Club Connectivity in Euthymic Bipolar Disorder
1,3
Author(s) and
Affiliation(s)
ABSTRACT
4
5
1,6
7
8
9
Stefani O’Donoghue , L. Kilmartin , D. O’Hora , L. Emsell , C. Langan, A. Leemans , B. Jeurissen , J.N. Forde , G.
10
11
1,2,3
1,3
Barker , P. McCarthy , D. M Cannon , and C. McDonald
1
2
Clinical Neuroimaging Laboratory, Departments of Psychiatry and Anatomy, College of Medicine, Nursing and
3
Health Sciences, Ireland and NCBES Galway Neuroscience Center, National University of Ireland Galway, Galway
4
5
Ireland. Department of Engineering, School of Engineering, NUI Galway. Department of Psychology, NUI
6
Galway. Translational MRI, Department of Imaging & Pathology, KU Leuven & Radiology, University Hospitals
7
8
Leuven, Belgium. Image Sciences Institute, University Medical Center Utrecht. Vision Lab, University of
9
10
Antwerp. Department of Psychiatry, University Medical Centre Groningen, the Netherlands. Institute of
11
Psychiatry, London Radiology, University College Hospital Galway
Introduction: Euthymic bipolar disorder has been relatively unexplored using complex network
1,2
analysis . Complex network analysis combines structural and diffusion magnetic resonance imaging
3,4
(MRI) to model the brain as a network and evaluate topological properties of brain structure . Most
recently, a group of highly inter-connected high density structures termed the ‘rich-club’ represents a
5
particular group of structures in integrated brain functioning . We hypothesized global
dysconnectivity as well as rich club effects to present as a feature of the disorder due to widespread
6,7
white matter microstructural alterations previously identified in this cohort .
Methods: This cohort of 42 individuals diagnosed with euthymic bipolar disorder and 43 healthy
volunteers underwent diffusion MRI scans. Network metrics were generated using the Brain
Connectivity Toolbox through MATLAB. Global metrics were derived to investigate properties of
integration. Metrics of degree, clustering coefficient, characteristic path length, global efficiency,
betweenness centrality and the rich club coefficient were investigated in this analysis.
Results: Analysis of global metrics revealed group differences across measures of characteristic path
length (p=0.017), global efficiency (p=0.015) and clustering coefficient (p=0.047). The rich club
connectivity effects were significant for k density values 55 and 56 before FDR multiple comparison
correction. k=55 (Z = -2.1571, p-value = 0.0296) & k= 56 (Z = -2.5288, p-value = 0.009801). After
correction of 28 p-values, k=56 demonstrated a trend effect. Rich club structural differences between
groups suggest impaired integration of the right superior frontal gyrus and left thalamus in the
bipolar group rich club network.
Discussion: Deficits in rich club connectivity in the bipolar group highlight the reduced capacity for
global brain communication, as suggested by the relationship detected between global efficiency and
rich club connectivity. Differentially affected rich club organization may explain for reductions in
whole brain communication.
References
1.Leow A, Ajilore O, Zhan L, et al. Biol. Psychiatry 2013;73(2):183-93. doi:10.1016/j.biopsych.2012.09.014.
2. Gadelkarim JJ, Ajilore O, Schonfeld D, et al. Hum. Brain Mapp. 2014;35(5):2253-64. doi:10.1002/hbm.22324.
3. Bullmore E, Sporns O. Nat. Rev. Neurosci. 2009;10(3):186-98. doi:10.1038/nrn2575.
4. Rubinov M, Sporns O. Neuroimage 2010;52(3):1059-69. doi:10.1016/j.neuroimage.2009.10.003.
5. Van den Heuvel MP, Sporns O. J. Neurosci. 2011;31(44):15775-86. doi:10.1523/JNEUROSCI.3539-11.2011.
6. Emsell L, Leemans A, Langan C, et al. Biol. Psychiatry 2013;73(2):194-201. doi:10.1016/j.biopsych.2012.09.023.
7. Emsell L, Langan C, Van Hecke W, et al. Bipolar Disord. 2013;15:365-376. doi:10.1111/bdi.12073.
Acknowledgements
This study was supported by funding from the Hardiman Research Scholarship. We gratefully acknowledge the
participants of this study and the radiographers of the University College Hospital Galway Magnetic Resonance
Imaging department for their support during data collection.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
AN EVALUATION OF A CONCUSSION EDUCATION PROGRAMME FOR YOUTH GAA ATHLETES AND
COACHES
Author(s) and
Affiliation(s)
Lindsay Sullivan and Michal Molcho
1
2
Discipline of Health Promotion and School of Health Sciences, NUI Galway
ABSTRACT
INTRODUCTION: Sports-related concussions are now recognized as a major public health concern,
and although more research is needed, the long-term effects from this injury are more widespread
than previously understood. Unfortunately, despite the association of concussion with short and
long-term health consequences many parents, coaches and young athletes still lack basic knowledge
about concussion and seem to believe that youth is a period of invincibility and that concussions may
be “toughed out” and do not require medical attention. AIMS: This proposed study aims to assess
self- reported prevalence of concussion among GAA players in the Republic of Ireland aged 13-18
years of age. This study also aims to examine self-reported knowledge, attitudes and concussion
reporting behaviours among youth GAA players and GAA coaches in the Republic of Ireland. A
concussion education programme will be implemented and its immediate and long-term impact will
be evaluated. METHODS: The proposed study will employ a concussion education programme based
on existing programmes. Various aspects of these programmes will be modified and improved.
Using a self-report questionnaire data will be captured on youth GAA athletes and coaches’
knowledge, attitudes and concussion reporting behaviours pre-intervention, immediately postintervention, 3-months post-intervention and 12-months post- intervention. These impact and
outcome evaluations will be conducted to assess the immediate and long-term impact of the
programme. CONCLUSION: Generating awareness of the severity and potential complications of
concussion, coupled with the promotion of safer attitudes towards this injury, could minimise the
number of players who return-to-play pre-maturely and promote a more safety-conscious sports
culture in Ireland.
References
1.
Acknowledgements
1,2
1,2
Acquired Brain Injury Ireland. Implications of concussion in sport. Submission to the Oireachtas Joint
Committee on Health and Children, October 2014. Available on:
http://www.oireachtas.ie/parliament/media/committees/healthandchildren/health2014/ABI-Ireland-Concussion-Submisison_Final_Oct_2014.pdf (Accessed: February 2015).
2. Kroshus, E., Baugh, C.M., Daneshvar, D.H., Viswanath, K. Understanding concussion reporting using a model
based on the theory of planned behaviour. J. of Adolesc Health, 2014; 54:269-274.
rd
3. McCrory, P., Meeuwisse, W., Johnston, K. Consensus Statement on Concussion in Sport, 3 International
Conference on Concussion in Sport, Held in Zurich, November 2008. Clin Sports Med., 2010; 19:185-200.
This study was supported by funding from the Irish Research Council (IRC).
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
GESTATIONAL WEIGHT GAIN AND SLEEP HYGIENE: RESULTS FROM A EUROPEAN PILOT CLINICAL
TRIAL OF LIFESTYLE INTERVENTION
1, 3
2
3
4
5
Sharon Conway , Fidelma P. Dunne , Collette Kirwan , David Simmons and Mireille N. van Poppel on behalf of
the DALI Core Investigator Group
1.
Author(s) and
Affiliation(s)
2.
3.
4.
5.
ABSTRACT
Health Behaviour Change Research Group, School of Psychology, National University of Ireland, Galway,
University Road, Galway, Ireland
School of Medicine, Clinical Science Institute, National University of Ireland, Galway, University Road,
Galway, Ireland
Health Research Board Clinical Research Facility Galway, National University of Ireland, Galway,
University Road, Galway, Ireland
Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, United Kingdom
Department of Public and Occupational Health, EMGO Institute for Health and Care Research, VU
University Medical Center, Amsterdam, The Netherlands.
Introduction: Obesity and excessive gestational weight gain (GWG) have been identified as
independent risk factors for maternal and foetal complications of pregnancy with significant lifelong
1
consequences. Data for pre-obese and obese women at-risk for Gestational Diabetes Mellitus
(GDM) receiving lifestyle intervention were assessed for adherence to ≤5kg study-specific GWG
recommendation, maternal characteristics analysed and neonatal outcomes assessed.
Design: Secondary data analysis was conducted on 104 European women aged between 18 and 42
2
years, with singleton pregnancy and Body Mass Index ≥29 kg/m . The raw dataset was derived from a
European pilot clinical trial entitled Vitamin D And Lifestyle Intervention for Gestational Diabetes
Mellitus Prevention (DALI*).
Methods: Weight (kg) and self-reported sleep (daily hours) were assessed at three study time-points:
baseline (pre-pregnancy to <20 weeks gestation), Visit 2 (24-28 weeks gestation) and Visit 3 (35-37
weeks gestation). Statistical tests of association and difference were conducted.
Results: 23% (n=24) of sample study population met study-specific GWG recommendation of ≤5kg.
At baseline, there were no significant differences from self-reported pre-pregnancy weight to
baseline screening Visit 1 weight between women who gained ≤5kg and those who gained >5kg, 1.18
kg and 1.37 kg respectively, p=0.837 (95% CI:-2.100, 1.708). From both baseline to Visit 2, and Visit 2
to Visit 3, significant differences were noted in GWG between women who adhered to GWG
recommendation and those who did not. At baseline, sample population daily mean hours slept were
7.8 hours. Women who adhered to ≤5kg GWG study recommendation over lifestyle intervention
period reportedly slept significantly more, on average 42 minutes more, p=0.036 (95% CI: 0.045,
1.276).
Conclusions: European-specific recommendations for optimal GWG should be ascertained. GWG
and sleep hours should be monitored and lifestyle intervention considered. Further research is
required to validate these findings as clinically meaningful.
References
1.
Artal, R., Lockwood, C.J., Brown, H.L. Weight Gain Recommendations in Pregnancy and the Obesity
Epidemic. Obstetrics & Gynecology, 2010, Volume 115: 152-155.
Acknowledgements
*Funding for the DALI study was received from the European Union 7 Framework Programme (FP7/2007-2013)
under grant agreement No.242187.
th
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
POSTER PRESENTATIONS
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
AN INTEGRATION OF PRECLINICAL TESTS TO ASSESS ACUTE ANXIOLYTIC AND CHRONIC
ANTIDEPRESSANT EFFECTS OF DESIPRAMINE IN RATS
1,2
Author(s) and
Affiliation(s)
ABSTRACT
Acknowledgements
1
1,2
Karen Bannerton , Rebecca Culkin , John P. Kelly
1
Discipline of Pharmacology and Therapeutics, School of Medicine, NUI, Galway
2
Galway Neuroscience Centre, NCBES, NUI, Galway
The rat forced swim test (FST) is the most widely used preclinical approach for evaluating
antidepressant efficacy. Although antidepressant effects appear following short-term treatment, this
does not reflect the clinical situation where chronic administration is required for therapeutic effects.
Furthermore, despite the high co-morbidity of depression and anxiety clinically, potential
antidepressants are not always assessed for their anxiolytic properties. Thus, this study aimed to
integrate preclinical tests of anxiety (elevated plus maze (EPM) and open field (OF)) and depression
(FST), in a single study design that would assess both acute anxiolytic, and chronic antidepressant
effects, using the standard antidepressant desipramine (DMI).
Male Sprague-Dawley rats received injections of either distilled water (control), or 2.5, 5 or 10 mg/kg
DMI. Thirty minutes after the first injection, the acute anxiolytic effects of DMI were assessed in the
EPM, followed immediately by the OF. Treatment was continued for a further 13 days, after which
the antidepressant effects in the FST were examined. Home cage locomotor activity was measured in
the hour preceding the test swim. Data were analysed using One-Way ANOVA, followed where
appropriate by post hoc SNK; p<0.05 was deemed statistically significant.
DMI had no acute anxiolytic effects in the EPM, and had no effect on distance moved (cm) in the OF.
In the FST, chronic DMI treatment significantly decreased immobility time and increased climbing
time in a dose dependent manner. Home cage locomotor activity was not altered, except for a
significant reduction in this parameter with DMI at 2.5 mg/kg.
Therefore, both anxiolytic and antidepressant behavioural parameters can be successfully integrated
into a single experimental design using the standard antidepressant desipramine. Further
investigation of this study design should be carried out using other well-validated anxiolytic and
antidepressant drugs, with the intention to use this approach for assessing novel compounds for
preclinical anxiolytic and/or antidepressant activity.
This project was funded by a postgraduate fellowship from the Discipline of Pharmacology and Therapeutics,
School of Medicine, NUI, Galway.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
A comparison of BMSCs and ADSCs and their potential effects in obesity.
Author(s) and
Affiliation(s)
C.L. Brougham, A. Lowery and M.J. Kerin.
Discipline of Surgery, NUI Galway.
ABSTRACT
Introduction: Adult mesenchymal stem cells (MSCs) are a subset of non-hematopoietic stromal cells
present in various adult tissues including bone marrow and adipose tissue. Bone marrow-derived
MSCs (BMSCs) and adipose-derived stem cells (ADSCs) possess the ability to differentiate into cells
such as fat, bone, cartilage as well as muscle, fibroblasts, ligament, tendon and stroma. Adipose tissue
is largely regulated by ADSCs. The secretion of autocrine and paracrine factors is essential for
progression along different lineages. In many ways BMSCs and ADSCs are similar, however, the
abundance of ADSCs which can be easily isolated proposes that ADSCs may be a preferred source of
stem cells which warrant investigation. In particular, ADSCs can be used in autologous cell therapy
which increases their possibilities as alternatives to BMSCs.
Aim:To investigate the effect of bone marrow-derived MSCs (BMSCs) and adipose-derived stem cells
(ADSCs) in obesity.
Methods:Following informed patient consent BMSCs and ADSCs were isolated from the iliac crest and
adipose tissue, respectively, of healthy volunteers. BMSCs and ADSCs were differentiated into
adipogenic, osteogenic and chondrogenic lineages. Conditioned media was harvested at various timepoints throughout these differentiation processes. Cytokine secretion was analysed by ELISA. miRNA
target prediction algorithms were employed to identify miRNAs of interest associated with stem cell
secreted cytokines. miRNAs of interest were analysed by RQ-PCR throughout the differentiation of
BMSCs and ADSCs.
Results: ADSCs and BMSCs differ in their differentiation potential. BMSCs display superior osteogenic
differentiation potential than ADSCs. ADSCs, however, showed a greater potential for adipogenic and
chondrogenic differentiation as quantified by Oil Red O Staining and toluidine blue staining,
respectively, compared to BMSCs. Both BMSCs and ADSCs exhibited similar expression levels of
secreted cytokines. miRNA prediction analysis identified various miRNAs of interest which potentially
target these secreted cytokines.
Conclusion:miRNA targeted therapy in ADSCs may provide future cell therapies for obesity.
References
1.Gimble, J.M. and Guilak, F., Differentiation potential of adipose derived adult stem (ADAS) cells.
Curr Top Dev Biol, 2003; 58:137-160.
2.Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A.,
Simonetti, D.W., Craig, S. and Marshak, D.R., ‘Multilineage Potential of Adult Human Mesenchymal
Stem Cells’, Science,1999; 284: 143-147.
3.Rodriguez, A.M., Elabd, C., Amri, E.Z., Ailhaud, G. and Dani, C., The human adipose tissue is a source
of multipotent stem cells. Biochimie 2005; 87(1): 125-8.
Acknowledgements
This study was supported by funding from the National Breast Cancer Research Institute (NBCRI).
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
LIFE WITHOUT MSCS? AN ANIMAL MODEL BASED ON FPA+ENDOGENOUS STROMAL CELL
ABLATION.
Author(s) and
Affiliation(s)
Camarillo E ., Duffy M. , O’Flynn L . Thompson K. , Canney M. , Dockery P. , Ceredig R. , Elliman SJ .
1
2
3
Orbsen Therapeutics Ltd , Regenerative Medicine Institute, NUI Galway, University Rd., Ireland and Anatomy
Department at NUI Galway , University Rd., Ireland eva.camarillo@orbsentherapeutics.com
ABSTRACT
Tissue-derived Mesenchymal Stromal Cells (MSCs) are comprised of a mixed population of fibroblastic
cells that can be isolated from bone marrow, placenta, adipose tissue and other tissues by adherence
to tissue culture plastic and formation of colony forming unit-fibroblasts (CFU-F). MSCs secrete potent
immune-modulatory and angiogenic factors and so represent a valid therapeutic option for
complicated inflammatory and ischemic diseases. Questions remain over the endogenous identity
and function of MSCs in vivo, as well as the heterogeneity and function of therapeutic MSCs
preparations in vitro. We have shown that antibodies against CD362 - a heparan sulphate
proteoglycan that mediates Left-Right patterning, extra cellular matrix (ECM) deposition and vascular
development in embryogenesis - can be used for the prospective isolation of highly enriched and
therapeutically active preparations of MSCs from multiple species. Fibroblast activation protein (FAP)
is a marker found in areas of active tissue remodelling and tumour-resident stromal cells that are
necessary for marrow and muscle homeostasis. To study the role of both proteins (CD362 and FAP) in
endogenous stromal cells will help understand their role in haematopoiesis (formation of blood
cellular components) which is disturbed in acute myeloid leukaemia (AML).
References
1
1.
2.
Acknowledgements
1
1
3
3
3
2
1
Kraman M, Bambrough J.P, Arnold N.J. Suppression of Antitumor. Immunity by Stromal Cells Expressing
Fibroblast Activation Protein– . Science, 2010, 330:827
Roberts E.W., Deonarine A., Jones J.O. Depletion of stromal cells expressing fibroblast activation
protein- from skeletal muscle and bone marrow results in cachexia and anemia. J. Exp. Med. 2013
Vol. 210 No. 6 1137-1151
This study was supported by funding from European Commission Seventh Framework Program Grant No. EU
FP7/315902. Marie Sklodowska-Curie Initial Training Networks. DeCIDE Decision-making within cells and
differentiation entity therapies
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Author(s) and
Affiliation(s)
ABSTRACT
References
Acknowledgements
Complement component C3a receptor blockade attenuates the liver regenration after partial
hepatectomy in LPS-hyporesponsive C3H/HeJ mouse
Rahiman Faiyaz1, Marlini Muhamad1, Beth Mallard1, Antony M. Wheatley1
1. Discipline of Physiology, National University of Ireland, Galway
The liver has a remarkable capacity to regenerate following exposure to toxins, infections or postsurgical excision [1]. Partial hepatectomy is the closest approximation of pure liver regeneration
unaccompanied by cellular injury and is the preferred in vivo model to study the regenerative response
[2]. Regeneration completes when the remnant lobes enlarge to the size of the original liver, a process
that typically requires about five to seven days in rat and mouse [3]. . Gut derived LPS is believed to
be involved in this mechanism. In the LPS-insensitive C3H/HeJ mouse, liver regeneration is delayed by
a mechanism believed to be other than the LPS-TLR4 pathway. Complement activation occurs
simultaneously with initiation of liver regeneration and leads to the generation of potent
inflammatory mediators, C3a and C5a. These anaphylatoxins may contribute to the early priming
stages of hepatocyte proliferation and therefore regulation of cytokine release and/or production, and
consequent induction of transcription factors require for regeneration. by acting on their respective
receptors expressed on liver cells.
C3H/HeJ (LPS-hyporesponsive) mice were used to establish the involvement of complement
component C3a in liver regeneration after partial hepatectomy. These mice were compared against
C3H/HeN (LPS-sensitive) mice, in which LPS/TLR-4 pathway is intact as opposed to C3H/HeJ mice. Both
the strains of mice were administered either with SB290157, a selective high affinity, competitive
antagonist of the anaphylatoxin C3a receptor at a dose of 1mg/kg of body weight [4][5] or vehicle
(phosphate buffered saline) alone via intraperitoneal injection 45 minutes prior to partial
hepatectomy. Repeated administration of SB290157 to ensure full receptor blockade was given to
animals every 24 hours until sample collection. Mice were euthanized after specific time points after
the surgery and regenerated liver weight was measured, and tissues were processed for further
analysis.
Liver weight – body weight ratios of untreated groups suggest that suggest that liver regeneration is
delayed in C3H/HeJ mice. But, liver mass restoration was significantly attenuated in C3H/HeJ mice at
3 and 7 days post hepatectomy when treated with C3a-receptor antagonist, SB290157. The proinflammatory cytokines IL-6, which aid the process of priming the hepatocytes into proliferation were
measured in the untreated groups. TNF-α level in C3H/HeJ mice was significantly lower in early-phase
time-points (1-hour and 3-hour) after hepatectomy. While Il-6 levels in untreated C3H/HeN mice
induced in a biphasic pattern peaking at 3-hour and 24 hours post hepatectomy, the IL-6 levels in
C3H/HeJ mice steadily rose, and were high at 24 hours post-hepatectomy supporting the delayed
response. Circulating C3a and C5a levels in blood were also measured in the untreated groups. The
levels were higher between 24 hours and 72 hours in both the strains of the mice when compared
against non-hepatectomised mice confirming the activation of complement after injury.
[1] R. Taub,. Nature Reviews Molecular Cell Biology, 2004, pp 5, 836–847.
[2] T.A. Zimmers., I.H McKillop., R.H Pierce., J.-Y. Yoo., L.G. Koniaris., Hepatology, 2004, pp 38, 326–
334.
[3] G.K. Michalopoulus “Liver Regeneration”, Science, 1997, pp 276(5309):60–6.
[4] A.F. Ducruet., B.E Zacharia., S.A Sosunov., P.R Gigante., M.L Yeh., J.W Gorski., M.L Otten., R.Y
Hwang., P.A DeRosa., Z.L Hickman., P. Sergot., E.S Connolly. PLoS One 7, 2012 [5] R.S Ames., D Lee., J.J
Foley., A.J Jurewicz., M.A Tornetta., W Bautsch., B Settmacher., A Klos., K.F Erhard., R.D Cousins., A.C
Sulpizio., J.P Hieble., McCafferty, G McCafferty., K.W Ward., J.L Adams., W.E Bondinell., Underwood,
D.C Underwood., R.R Osborn., A.M Badger., H.M Sarau. J. Immunol, 2001, pp166, 6341–6348.
The “James Hardiman scholarship, NUIG” is thanked for the academic funding of Rahiman Faiyaz’s PhD program
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
The Role of DNA Methylation in the Regulation of NOD-Like Receptor Expression and Activity.
Author(s) and
Affiliation(s)
Claire L. Feerick and D.P. McKernan
1
Discipline of Pharmacology and Therapeutics, School of Medicine, NUI Galway.
ABSTRACT
NOD-like receptors (NLRs) are a class of pathogen recognition receptors involved in the innate
(1)
immune response . Upon stimulation, these receptors promote the production of pro-inflammatory
(2)
cytokines . DNA methylation, carried out by DNA Methyltransferases, is an epigenetic modification
(3)
shown to modify gene expression . Regulators of NLR expression are currently unknown. We
hypothesise that DNA methylation may play a role.
Our objective was to investigate basal NOD1/NOD2 expression and activity following DNA
Methyltransferase inhibition. Basal expression was quantified in THP-1 monocytic and HCT116
intestinal epithelial cell lines following exposure to 5µM 5-Azacytidine and 500nM 5-Aza-2Deoxycytidine. Pro-inflammatory activity was investigated by stimulating 5-Azacytidine or 5-Aza-2Deoxycytidine pre-treated cells with iE-DAP (NOD1 ligand) or MDP (NOD2 ligand) and subsequently
quantifying pro-inflammatory cytokine expression. Gene expression analysis was carried out by
quantitative polymerase chain reaction (qPCR). Protein expression was analysed by western blotting.
One-way ANOVA or two-way ANOVA analsysis was carried out where appropriate, followed by
suitable post-hoc tests.
In THP-1 cells, 5-Azacytidine significantly increased NOD1 (p<0.001) and NOD2 (p<0.01) expression; 5Aza-2-Deoxycytidine significantly increased NOD2 expression (p<0.001). In HCT116WT cells, 5Azacytidine did not significantly alter NOD1/NOD2 expression (p>0.05); 5-Aza-2-Deoxycytidine
significantly increased NOD2 expression (p<0.001). Pre-treatment of THP-1 cells with 5-Azacytidine
for 72 hours was found to significantly increase TNF-α expression in response to stimulation with
NOD1 (p < 0.001) or NOD2 (p < 0.001) ligands. Similarly, IL-6 expression in pre-treated cells
significantly increased in response to NOD1 (p < 0.01) or NOD2 (p < 0.05) ligands.
This study has uncovered, for the first time, a relationship between methylation and NOD-Like
Receptor expression and activity, suggesting that DNA methyltransferase enzymes could play a key
role in the regulation of these pathogen recognition receptors and so their inhibitors could potentially
be used to control the innate immune response.
References
1) Kanneganti, T. D., Lamkanfi M. and Nunez G. Intracellular NOD-like receptors in Host Defense and Disease.
Immunity, 2007; 27(4): 549-559.
2) Chen, G., Shaw M. H., Kim Y. G. and Nunez G. NOD-Like Receptors: Role in Innate Immunity and Inflammatory
Disease. Annu Rev Pathol., 2009; Vol. 4: 365-98.
3) Yu, N. K., Baek, S. H. and Kaang B. K. DNA- methylation-mediated control of learning and memory. Mol Brain,
2011; 4: 5.
This study was supported by funding from the Hardiman Scholarship.
Acknowledgements
1
1
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Author(s) and
Affiliation(s)
ABSTRACT
CHARACTERIZATION OF THE ENDOCANNABINOID SYSTEM IN THE DESCENDING PAIN PATHWAY IN
A MOUSE MODEL OF IFN-α-INDUCED HYPERALGESIA
Marie Fitzgibbon
1
2
1, 3
1, 3
1, 2, 3
, R.J. Henry , D.M. Kerr
2, 3
, D.P. Finn , M. Roche
1, 3
3
Physiology, Pharmacology and Therapeutics, School of Medicine, NCBES Galway Neuroscience Centre and
Centre for Pain Research, National University of Ireland Galway, Ireland
Introduction: Interferon-alpha (IFN-α) is a pro-inflammatory cytokine used to treat cancers and
infections. However, its use is associated with depression and painful symptoms [1, 2]. Studies in our
lab have demonstrated that repeated administration of IFN-α to mice results in depressive-like
behaviour and enhanced nociceptive responding in the formalin test [3]. The endocannabinoid
system plays an important role in emotional and nociceptive processing, however it is unknown
whether IFN-α administration alters this system, which may underlie the behavioural changes
observed.
Aims and Objectives: This study investigated the effect of repeated IFN-α administration on
endocannabinoid levels and CB1 receptor expression in the descending pain pathway. Furthermore,
this study examined if endocannabinoid levels in these regions during expression of nociceptive
behaviour differed between saline- and IFN-α treated animals.
Methods: Male C57Bl/6J mice were administered human (h)IFN-α (Roferon-A: 8,000 IU/g s.c.) or
saline daily for 8 days. 24 hours following the final treatment, a subset of animals were sacrificed and
the periaqueductal gray (PAG), rostral ventromedial medulla (RVM) and spinal cord dissected out,
snap-frozen and stored at -80°C. A further subset of animals received an intraplantar injection of
formalin (1%; 20µl) into the left hind paw and nociceptive behaviour was recorded for 35 minutes,
before sacrifice. Concentrations of the endocannabinoids anandamide (AEA) and 2arachidonylglycerol (2-AG) were determined using LC-MS-MS and expression of CB1 using
quantitative RT-PCR.
Results: IFN-α enhanced formalin-evoked nociceptive responding throughout the late phase of the
test compared with saline-treated counterparts. AEA or 2-AG levels did not differ between saline or
IFN-α-treated animals. However, in IFN-α-treated animals that received formalin, 2-AG levels in the
PAG and RVM; and AEA levels in the RVM; were increased compared to non-formalin treated
counterparts, an effect not observed in saline-treated. There was no change in CB 1 expression
between IFN-α- and saline-treated animals.
Discussion and Conclusion: Repeated IFN-α enhances nociceptive responding, an effect associated
with increased 2-AG and AEA levels in key regions of the descending pain pathway. This indicates that
alterations in the endocannabinoid system in the descending pain pathway may underlie IFN-αinduced hyperalgesia.
References
1.Raison, C.L., et al., Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS
Drugs, 2005. 19(2): p. 105-23.
2.Shakoor, A., et al., Frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin for
chronic hepatitis C. J Ayub Med Coll Abbottabad, 2010. 22(4): p. 6-9.
3. Fitzgibbon M., et al., Enhanced inflammatory pain behaviour in the interferon-alpha induced mouse model of
th
depression. Proceedings of the International Association for the Study of Pain 15 World Congress on Pain,
2014. P2: 06.
Acknowledgements
This study was supported by funding from Molecular Medicine Ireland Clinical & Translational Research Scholars
Programme and Science Foundation Ireland Research Frontiers Project (Grant no. 11/RFP/NES/3175).
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
TLR3-INDUCED INFLAMMATORY RESPONSES IN THE HYPOTHALAMUS ARE ATTENUATED
FOLLOWING FAAH, BUT NOT MAGL, INHIBITION; AN EFFECT INDEPENDENT OF SEX
Author(s) and
Affiliation(s)
Lisa Flannery , Rebecca Henry , Daniel Kerr
1,2
1
1,3
2
1,2,3
2,3
, David P. Finn , Michelle Roche
1,3
3
Physiology and Pharmacology and Therapeutics, School of Medicine, NCBES Centre for Pain Research and
Galway Neuroscience Centre, National University of Ireland Galway, Ireland
ABSTRACT
Viral antigens are recognised by various toll-like receptors (TLRs) including TLR3, activation of which
induces both systemic and central inflammatory responses. Recent evidence has demonstrated that
both synthetic cannabinoids and enhancing endogenous cannabinoid tone can modulate TLR31,2
induced inflammatory responses . However, it is unknown if sexual dimorphic effects exist in
endocannabinoid modulation of TLR3-induced inflammatory responses. Thus, the aim of this study
was to investigate if enhancing 2-AG or anandamide tone modulates TLR3-induced inflammatory
responses and if these responses differ between males and females.
Male and Female Sprague-Dawley rats were systemically administered the MAGL inhibitor MJN110
(5mg/kg) or the FAAH inhibitor URB597 (1mg/kg), 1 hour or 30mins respectively, prior to the systemic
administration of the TLR3 agonist poly I:C (3mg/kg). A further group received vehicle
(ethanol:cremophor:saline; 1:1:18) followed 30min later by systemic poly I:C/saline administration.
Animals were sacrificed 4hrs post poly I:C challenge, spleen and hypothalamus were excised and
O
stored at -80 C. Concentrations of the endocannabinoids were determined using LC-MS-MS and
inflammatory gene expression was determined using qRT-PCR.
Systemic administration of MJN110 increased 2-AG levels in the spleen and hypothalamus of both
males and females; while URB597 increased anandamide levels. Poly I:C increased IP-10, IRF7, IĸBα
and TNF-α expression in the spleen of males and females; an effect not altered by MJN110 or
URB597. In the hypothalamus, poly I:C increased IP-10, IRF7 and TNF-α expression in both male and
female rats. URB597, but not MJN110, attenuated this poly I:C-induced increase in the hypothalamic
expression of IRF7 and TNF-α in males and IP-10 and IRF7 expression in females.
This data supports an important sex independent role of FAAH substrates in the modulation of TLR3induced inflammatory responses in the hypothalamus, a key site involved in mediating the
neuroendocrine and sickness response to infection.
References
1. Downer E.J., Clifford E., Gran B., Nel H.J., Fallon P.G., Moynagh P.N. Identification of the Synthetic
Cannabinoid R(+)WIN55,212-2 as a Novel Regulator of IFN Regulatory Factor 3 Activation and IFN-β
Expression: RELEVANCE TO THERAPEUTIC EFFECTS IN MODELS OF MULTIPLE SCLEROSIS. J. Biol. Chem., 2011;
286(12): 10316-10328.
2. Henry R.J., Kerr D.M., Finn D.P., Roche M. FAAH-mediated modulation of TLR3-induced neuroinflammation in
the rat hippocampus. J. Neuroimmunol., 2014; 276(1-2): 126-134.
Acknowledgements
This study was supported by funding from the Hardiman Postgraduate Scholarship, the Discipline of Physiology
and by Science Foundation Ireland Research Frontiers Project (Grant no. 11/RFP/NES/3175).
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
INCREASING FATTY ACID AMIDE HYDROLASE SUBSTRATES ATTENUATES TLR4-INDUCED
NEUROINFLAMMATION INDEPENDENT OF CENTRAL CANNABINOID RECEPTOR ACTIVATION
1,3
Author(s) and
Affiliation(s)
ABSTRACT
1,2,3
2,3
1,3
Rebecca J. Henry , Daniel M. Kerr , David P. Finn , Michelle Roche
3
Physiology and Pharmacology and Therapeutics, School of Medicine, NCBES Centre for Pain Research and
Galway Neuroscience Centre, National University of Ireland, Galway, Ireland.
1
2
Introduction: Enhanced endocannabinoid tone modulates neuroinflammatory responses
and thus may provide a potentially novel therapeutic target for neurodegenerative and
psychiatric disorders. Accordingly, recent data have demonstrated that inhibition of the
anandamide (AEA) hydrolytic enzyme FAAH, attenuates neuroinflammatory responses
following TLR3 or TLR4 activation1 2. However, the precise receptor mechanisms
underpinning these effects are not fully elucidated. This study examined if attenuation of
TLR4-induced neuroinflammation following FAAH inhibition was mediated by
endocannabinoid receptor targets within the brain
Methods: Rats received an acute microinjection of either the CB1 receptor, CB2 receptor,
PPARγ or the PPARα antagonist (AM251, AM630, GW9662 or MK886, respectively), 15
minutes prior to systemic administration of the FAAH inhibitor PF3845. Thirty minutes post
PF3845; animals received systemic administration of LPS and were sacrificed 2h later.
Frontal cortical tissue was excised and expression of NFkB-inducible inflammatory genes
were determined using qRT-PCR. Concentration of AEA, PEA and OEA were determined
using LC-MS-MS. MAPK/ERK activation was examined using western immunoblot analysis.
Data were analysed using one-way ANOVA followed by Fisher’s LSD post-hoc test or
unpaired two-tailed t-test. p < 0.05 was deemed significant.
Results: PF3845 increased AEA, PEA and OEA levels in the frontal cortex, an effect
associated with an attenuation of LPS-induced increases in expression of IkBα and NFkBinducible genes IL-1β, IL-6, TNFα and IL-10. Central administration of AM251, AM630,
GW9662 or MK886 failed to affect the PF3845-induced attenuation of cytokine expression
following LPS. Furthermore, PF3845 failed to alter pERK1/2 expression when compared to
vehicle-LPS counterparts.
Summary & conclusion: Increasing FAAH substrate levels in the brain potently attenuates
TLR4-induced neuroinflammatory responses. These effects do not appear to be mediated via
activation of central cannabinoid receptors or PPARs. Further research is required in order
to decipher the central receptor and/or molecular mechanisms mediating the potent antiinflammatory effects of FAAH substrates in the brain
1
References
Henry RJ et al. FAAH-mediated modulation of TLR3-induced neuroinflammation in the
hippocampus. J Neuroimmunol., 2014; Nov 15;276(1-2):126-34
2
Kerr DM et al. Pharmacological inhibition of endocannabinoid degradation modulates the
expression of inflammatory mediators in the hypothalamus following an immunological
stressor. Neuroscience 2012 Mar 1;204:53-63
Acknowledgements
Funding provided by Science Foundation Ireland Research Frontiers Project (Grant no.
11/RFP/NES/3175).
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
PHYSIOLOGICAL RESPONDING OF THE STRESS SENSITIVE WKY RAT IN RESPONSE TO TLR4
ACTIVATION
1
1, 3
1, 2, 3
1
1
1, 3
Author(s) and
Affiliation(s)
Marykate Killilea , L. Flannery , D. M. Kerr
, B. L. Mallard , A. M.Wheatley and M Roche
1
2
3
Physiology and Pharmacology and Therapeutics, School of Medicine, NCBES Centre for Pain
Research and Neuroscience Centre, National University of Ireland, Galway, Ireland.
ABSTRACT
Stress is known to be a predisposing factor in and/or exacerbate a host of medical conditions, the
response to which is determined by genetic factors. The Wistar Kyoto (WKY) rat is a genetically stresshypersensitive strain of rat which exhibits an anxiety- and depressive-like phenotype. Although recent
1,
data demonstrates enhanced expression of toll-like receptors (TLRs), in the WKY rat , it is unknown if
this rat strain exhibits altered physiological responding to an immunological stressor This study
examined the effect of acute administration of the bacterial endotoxin and TLR4 agonist
lipopolysaccharide (LPS), on locomotor activity, pro-inflammatory cytokine levels and activation of
the hypothalamic-pituitary-adrenal (HPA) axis in WKY rats in comparison to the less stress-sensitive
Sprague-Dawley (SD) strain.
The data revealed that WKY rats exhibit reduced home cage locomotor activity when compared to SD
counterparts. Systemic administration of LPS or saline increased locomotor activity of all animals in
the 30 minute time period post-injection, an effect significantly blunted in WKY rats. Locomotor
activity of SD LPS-treated rats was significantly reduced in between 90-150 minutes post
administration when compared to saline-treated counterparts, an effect not observed in WKY rats..
Assessment of pro-inflammatory cytokine levels revealed that LPS significantly increased IL-1β levels
in liver and mRNA expression in the hypothalamus of both SD and WKY when compared with salinetreated counterparts. Furthermore, LPS significantly increased plasma corticosterone levels in SD
rats, an effect blunted in WKYs rats. Taken together, WKY and SD rats exhibit similar central and
peripheral pro-inflammatory but not corticosterone responses to TLR4 activation. Thus, WKY rats
exhibit an altered HPA axis in response to an immune stress, an effect which may underlie the stresssensitive behavioural profile of these animals.
References
Acknowledgements
1.
McKernan DP, Nolan A, Brint EK, O’Mahony SM, Hyland NP, et al. (2009) Toll-Like Receptor
mRNA Expression Is Selectively Increased in the Colonic Mucosa of Two Animal Models
Relevant to Irritable Bowel Syndrome. PLoS ONE 4(12): e8226.
This work was supported by the College of Medicine, postgraduate fellowship and Discipline of Physiology, NUI
Galway
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
INVESTIGATION OF THE EFFECTS OF THE TLR3 AGONIST POLY I:C ON SYNAPTIC TRANSMISSION AND
AXONAL TRANSPORT IN CELL CULTURE MODELS OF PARKINSON’S DISEASE
Author(s) and
Affiliation(s)
Laura Olsen and D. McKernan
Discipline of Pharmacology and Therapeutics, School of Medicine
ABSTRACT
Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor dysfunctions
(resting tremors, unstable posture, bradykinesia, and rigidity) and sometimes dementia.
Dopaminergic (DA) neurodegeneration in the substantia nigra causes cortical-striatal motor pathway
impairment in PD. This neurodegeneration is correlated with alpha-synuclein aggregation, oxidative
stress, and chronic neuroinflammation. Toll-like receptor 3 (TLR3) recognizes pathogen-associated
molecular patterns (PAMP), specifically viral nucleotides. Neuronal TLR3 activation leads to
proinflammatory cytokine expression and microglia activation. This type of neuroinflammation is
characteristic of PD. Also, chronic viral infection has been identified as a risk factor for developing PD.
Further investigation into this innate immune response in neurons is needed to determine the role of
neuroinflammation in PD pathology. Thus far, animal models using neurotoxins such as 6hydroxydopamine (6-OHDA) and rotenone have investigated the role of TLRs. This study attempts to
replicate these PD models in vitro with specific interest the effects of TLR3 activation prior to
neurotoxin administration.
The effects of TLR3 activation on degeneration in the presence of 6-OHDA and rotenone were
assessed. SH-SY5Y cells and rat primary co-cultures cells were used. Cellular activity and
synaptic/axonal transport proteins were examined using cell death assays, Western Blot and PCR.
Dose response cell death assays were performed for poly I:C (0-100 µg/ml), 6-OHDA (0-50 µM), and
rotenone (0-500 nM). Poly I:C (20 µg/ml), 6-OHDA (20 µM), and rotenone (250 nM) alone lead to
alterations in synaptic and axonal transport proteins. Pre-treatment with poly I:C was found to be
neuroprotective or increase neurodegeneration depending on the cellular environment following PD
related neurotoxin treatment. These disparities may be due to the downstream effects of TLR3
activation (cytokine expression and NF-кB nuclear translocation). Neuroprotective inflammatory
processes may instead lead to exacerbation of neurodegeneration in PD due to the changes in the
microenvironment for DA neurons.
Acknowledgements
Department of Pharmacology
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
Regulating immunogenicity and tolerogenicity of BMDCs through modification of cell surface
glycosylation
ABSTRACT TITLE
1
2
1,2
1
1
1
2
Kevin Lynch , Heidi Annuk , Jared Gerlach , Lisa O’Flynn , Aideen Ryan Paul Lohan , Michelle Kilcoyne ,
2
1
Lokesh Joshi , Thomas Ritter .
Author(s)
Affiliation(s)
and
1
Regenerative Medicine Institute (REMEDI), College of Medicine, Nursing & Health Sciences, National
University of Ireland, Galway.
2
Glycoscience Group, NCBES National Centre for Biomedical Engineering Science, National University of
Ireland, Galway.
ABSTRACT
Introduction
Sialic acids (Sias) are a broad family of negatively-charged, nine-carbon monosaccharides involved in a
vast array of immune cell functions. In order to elucidate the functional consequences of removal or
addition of Sia to/from the surface of rat bone marrow dendritic cells (BMDCs), we investigated the
role of Sia in BMDC immunoregulatory function in an allogenic setting.
Methods and Materials
BMDCs isolated from the bone marrow of Dark Agouti rats were cultured in media supplemented
with GM-CSF and Interleukin-4 for 10 days and subjected to neuraminidase (Neura) treatment or
dexamethasone (Dexa) treatment. BMDCs were analysed by flow cytometry, lectin microarray, RTPCR and in allogenic functional assays.
Results
Dexa-BMDCs showed changes in their glycosylation pattern compared to untreated BMDCs when
profiled by lectin microarray, including an increase in SNA-I binding intensity which suggested
increased sialylation. Cell surface increases in Sias were also supported by lectin coupled flow
cytometry. Subsequent neuraminidase treatment of BMDCs resulted in stronger proliferation of
allogenic lymphocytes compared to untreated BMDCs and Dexa-BMDCs when assayed in allogeneic T
cell proliferation/activation assays, indicating the importance of Sias in BMDCs’ ability to stimulate
allogenic lymphocytes. Dexa-treated BMDCs show increased anti-inflammatory and decreased proinflammatory cytokine mRNA expression even in the context of an inflammatory microenvironment.
Conclusions
This study points toward the potential of DC surface sialylation as a therapeutic target to improve and
diversify DC-based therapies and treatments. In the context of disease, cell glyco-engineering could
have particular positive implications in BMDC-based vaccines, the tumour microenvironment and
transplant biology.
Acknowledgements
The authors are supported by research grants from Science Foundation Ireland (Grant Numbers 12/IA/1624 and
12/TIDA/B2370 and by the European Union Regional Development Fund.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
Serotonergic receptor functionality in the olfactory bulbectomized (OB) rat model of depression.
Z McAleavey1,2 JP Kelly1,2
Author(s) and
Affiliation(s)
1
Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway
Galway Neuroscience Centre, National University of Ireland Galway
2
ABSTRACT
Depression is a common neuropsychiatric disorder of which the OB model is a well validated model.
As well as behavioural alterations this model also exhibits changes in the serotonergic (5-HT) system,
including 5-HT1A and 5-HT2a receptor alterations. However to our knowledge, few studies have looked
at the functionality of these receptors in this model. Thus, the aim of this study was to assess the
functionality of these two receptors using the selective 5-HT1A agonist 8-hydroxy-2-(di-npropylamino)-tetraline (8-OH-DPAT) and the selective 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI).
Bilateral OB (or sham surgery) was performed on young male Sprague-Dawley rats. At 4 weeks postsurgery, the animal’s baseline homecage locomotor activity was monitored for 2 hours and after this
they received an acute injection of DOI (0.3, 1 or 3 mg/kg) or 8-OH-DPAT (0.1, 0.25 or 0.5 mg/kg), and
monitored for a further 2 hours. Locomotor activity was measured using EthoVision® videotracking
software. Data were analysed using Two-Way ANOVA, followed by a One-Way ANOVA and StudentNewman Keuls post–hoc analysis where appropriate, p<0.05 was considered significant.
OB animals treated with 3 mg/kg DOI displayed greater homecage locomotor activity than their sham
equivalents (p<0.05). The same pattern was evident in OB animals treated with 0.5 mg/kg 8-OHDPAT, with the locomotor activity being greater compared to their sham equivalents (p<0.05). A dose
response was also evident in the OB treated animals with those treated with 0.5 mg/kg of 8-OH-DPAT
moving significantly more than those treated with 0.1 and 0.25 mg/kg (p<0.05).
The above results provide evidence for a heightened sensitivity of both the central 5-HT1A and 5-HT2A
receptors in the OB model. Given that there are suggestions of supersensitivity of these receptors in
clinical depression, these results provide further credence to the OB rat as a model of this condition .
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
IMPACT OF PRENATAL OR POSTNATAL EXPOSURE TO METHAMPHETAMINE ON ADULT BEHAVIOUR
IN RATS
Author(s) and
Affiliation(s)
1,2
Kate McDonnell-Dowling
and J.P. Kelly
1,2
1
Discipline of Pharmacology and Therapeutics, College of Medicine, NUI, Galway, Ireland
2
Galway Neuroscience Centre, National Centre for Biomedical Engineering Science, NUI, Galway, Ireland
In recent years methamphetamine (MA) has become more popular as a drug of abuse among women
ABSTRACT
of childbearing age and hence MA abuse in pregnant/lactating women is becoming an increasingly
prevalent issue. There are few preclinical studies investigating MA’s potential harm at these different
exposure times and even fewer studies have examined the effects in later life after prenatal or
postnatal exposure in offspring. Thus, the aim of this study was to determine if prenatal or postnatal
MA exposure in rats at a pharmacological dose affects behaviour in adult life. Pregnant SpragueDawley dams (n=8-10 dams/group, 250-300g) received MA (3.75mg/kg) or control (distilled water)
daily via oral gavage either from gestation day 7-21 or postnatal day (PND) 1-21. Later in life, a range
of well-recognised behavioural parameters were examined in the offspring including paradigms of
anxiety, depression, cognitive function and locomotor activity during the adolescent and adult
periods. Data were analysed using either Repeated-Measures ANOVA and Two-way ANOVA or
Friedman’s ANOVA and Kruskal-Wallis with relevant post-hoc tests, with the level of significance set
at p<0.05. No significant impairments were observed in the adolescent or adult measures of anxiety,
cognitive performance or locomotor activity. In the adult period however the postnatal MA male (but
not female) group displayed significantly decreased time spent immobile and increased time spent
climbing in the forced swim test (i.e. less “depressive-like” behaviour). There was also a trend for the
prenatal MA male group that showed increased time spent immobile and decreased time spent
climbing (i.e. more “depressive-like” behaviour). This study demonstrates that MA can have a
profound long lasting effect on rats that are exposed to the drug via the breast milk. If extrapolated
to the clinical scenario, this will give cause for concern regarding the risks associated with this drug of
abuse during the postnatal period.
Acknowledgements
This study was supported by funding from a PhD fellowship awarded by the College of Medicine, NUI, Galway,
Ireland.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
PRE-ACTIVATION OF RECIPIENT-DERIVED MESENCHYMAL STEM CELLS (MSCS) ENHANCES THEIR
IMMUNOSUPPRESSIVE PROPERTIES
Author(s) and
Affiliation(s)
Nick Murphy , Oliver Treacy , Aideen Ryan , Paul Lohan , Kevin Lynch , Matthew Griffin , Thomas Ritter
1
1
1
1
1
1
1
1
School of Medicine, Nursing and Health Sciences, NUI Galway
ABSTRACT
Pre-activating MSCs with pro-inflammatory cytokines may enhance their immunosuppressive
properties creating, potentially, a more potent immunotherapy for inflammatory diseases and solid
organ transplantation. We have previously shown that recipient derived(syngeneic) MSCs fail to
prolong allograft survival in a rat model of corneal transplantation. Therefore, we investigated if pretreating syngeneic MSCs could enhance their immunosuppressive effects. Syngeneic(Lewis) rat MSCs
were cultured with recombinant cytokines IFN-γ, TNF-α, and/or IL-1β for 72 hours. Following
activation, MSC production of inducible nitric oxide which suppresses T cell responsiveness, was
measured by Griess assay and IL-10, PD-L1 and IL-6 were measured by RT-PCR analysis. Furthermore,
activated MSCs were co-cultured with lymphocytes to assess their ability to inhibit T cell proliferation.
Production of nitric oxide was significantly increased in MSCs pre-treated with TNF-α/IL-1β and IFNγ/TNF-α/IL-1β. These combinations also significantly inhibited T cell proliferation(CD4-12.9%;CD813.08% and CD4-13.1%;CD8 12.9%, respectively) compared to untreated MSCs(CD4-91.3%;CD882.8%, p<0.001). RT-PCR analysis showed that IL-10, PD-L1 and IL-6, which are involved in inhibition
of dendritic cell maturation and T cell proliferation, as well as Treg induction, were up-regulated in
cytokine pre-treated MSCs. Pre-activation of MSCs induces a strong immunosuppressive phenotype
by up-regulating production of immunosuppressive factors, thereby creating a more potent
immunotherapy compared to their untreated counterparts.
References
Treacy, O., O'Flynn, L., Ryan, A. E., Morcos, M., Lohan, P., Schu, S., Wilk, M., Fahy, G., Griffin, M. D., Nosov, M.
and Ritter, T. (2014), Mesenchymal Stem Cell Therapy Promotes Corneal Allograft Survival in Rats by Local and
Systemic Immunomodulation. American Journal of Transplantation, 14: 2023–2036. doi: 10.1111/ajt.12828
Acknowledgements
This study was supported by funding from Science Foundation Ireland (SFI)
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
CONCANAVALIN A-INDUCED ACUTE LIVER INJURY AND INTESTINAL PERMEABILITY IN MICE
Author(s) and
Affiliation(s)
Hairulhisyam M. Ngatiman , M. Marlini , B. Mallard , P. Dockery , AM. Wheatley
1
1
2
1
1
2,3
1
3
Discipline of Physiology Anatomy, School of Medicine and Cente of Microscopy and Imaging, NUI Galway
ABSTRACT
Acute liver failure (ALF) is a syndrome, which result in a rapid loss of hepatic function. It features
multiple organs failure clinically and in animal models. Acute liver failure can develop from several
conditions, including viral hepatitis, a drug/toxin/chemical-induced injury or autoimmunity The initial
events in autoimmune or viral hepatitis are the stimulation of T cells and the activation of
macrophages. However, the liver becomes the target of a misdirected and excessive immune
response. Intravenous administration of Concanavalin (Con) A in mice provides a chemical-induced
1
experimental model for immune-mediated liver injury . It has recently been demonstrated that an
LPS receptor (Toll-like receptor 4, TLR4) is essential for the development of Con A injury and the injury
involves increased gastrointestinal permeability. Treatment of male, C3H/HeN mice with Con A
(30µg/g i.v.) resulted in liver injury as evidenced by increased activity of alanine aminotransferase
(ALT) in plasma and hepatocellular necrosis. Treatment of male, C3H/HeJ mice with Con A (25µg/g i.v)
to observe LPS insensitivity, and this was accompanied by reductions in plasma ALT activity and
hepatocellular necrosis at 24 h after Con A treatment. In everted gut sac experiments, transjejunal
clearance of FITC Dextran (4kD MW) was increased 1 hour after treatment in C3H/HeN. The clearance
was reduced to near background level in gut sacs prepared from C3H/HeJ mice. Mice insensitive of
LPS-TLR4 signalling pathway had reduced ALT activity 24 h after Con A administration compared with
wild-type animals. However, transjejunal clearance in wild-type was increased. These results indicate
Con A-induced intestinal permeability is a key role for LPS-TLR4 pathway activation in acute liver
injury.
References
1.
Acknowledgements
This study was supported by funding from SLAI, Ministry of Education Malaysia
Pusztai, A. Characteristics and consequences of interactions of lectins with the intestinal mucosa. Arch
Latinoam Nutr., 1996; 44:10S-15S.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
TITLE
Authors &
Affiliations
ABSTRACT
DNA replication in the presence of Cdc7 inhibition in human breast cells
1,2
1,2
1,2
Quach Thi Thu, H. , Rainey, MD . and Santocanale, C .
1
2
Centre for Chromosome Biology (CCB) and National Centre for Bioengineering and Sciences (NCBES); School of
Natural Sciences; National University of Ireland Galway; Galway, Ireland
Background: Breast cancer is one of the most popular malignant solid tumours in Western women and considered
as the second leading cause of cancer death in Ireland [1]. Effects of hormonal and chemical therapies which focus
on ER/PR/HER2 receptors were proved, but treatment options for triple-receptor negative (ER-/PR-/HER2-) breast
cancer are limited. Recently, inhibition of cell growth by targeting to DNA replication becomes one of the
potential targets of chemotherapy for breast cancer treatment.
DNA replication is a critical event by which an original DNA duplicates to produce two identical copies. It occurs in
S-phase of cell cycle and requires a cooperation of many enzymatic proteins, including CDC7 and CDK kinases.
CDC7 is a Ser/Thr kinase enzyme which involves in many cellular processes, especially in DNA replication [2].
Depletion of CDC7 causes a blockade of S-phase progress and leads to apoptotic cell death without inducing any
DNA damage response [3]–[5]. Based on this fact, many CDC7 inhibitors were generated, including a selective
CDC7 inhibitor XL413 and a dual-effect CDC7/CDK9 inhibitor PHA767491 [3], [6]. We hypothesise that inhibition of
CDC7 kinase restrains breast cancer cell proliferation and survival by targeting the initiation and licensing of DNA
replication.
Methods: To examine the effects of Cdc7 inhibition, a non-malignant breast cell line, MCF10A (p53-wild type) and
a breast cancer cell line, MDA-MB-231 (p53-mutant) were employed. Both cell lines were treated with drugs
(XL413/PHA767491) for a short-term (24 hours) and long-term (24-48-72 hours) treatments and harvested for
biochemical assays, including FACS (flow cytometry), WB (Western Blotting) and DNA fiber.
Results: After 24h treatment with XL413, apoptotic cell death is undetectable. Both cell lines continue to grow
while CDC7 is inhibited in a long-term treatment (24-48-72hr). These events are confirmed by the incorporation
of EdU (5-ethynyl-2’-deoxyuridine, a nucleoside analogue of Thymidine) to active unwound DNA during S-phase,
even with high doses (25 and 50µM XL413). The failure of blocking DNA replication is also demonstrated by
observing replication fork patterns after the short-term treatment. Investigating effects of CDC7 inhibition on
synchronised G1/S phase cells revealed a delay of DNA synthesis at S phase while cells are treated with XL413.
However, cells are still able to go through G2 and enter M phase. In contrast, with PHA767491 treatment, these
effects were not observed. No S-phase cells are recorded after 24h treatment with this drug. Treated cells
accumulate at G2 phase and only a minor proportion of mitotic MDA-MB-231 cells can enter S phase in the
presence of PHA767491.
Discussion: CDC7 inhibition by XL413 slows down the rate of S-phase progress, attenuates cell growth and inhibits
survival rate of breast cancer cells. However, it cannot prevent cells entering M-phase as well as pass through G1
to enter S-phase. In contrast, CDC7 inhibition by PHA767491 totally blocks DNA synthesis, ceases cell proliferation
and prevents cancer cells entering M-phase or S-phase. The difference between the effects elicited by the two
compounds might be related to off-target effects. These data may suggest that fully specific CDC7 kinase
inhibitors might not be efficacious in breast cancer treatment and have profound implications for the clinical
development of emerging CDC7 inhibitors
References
[1]National Cancer Registry Ireland, 2014,” 2014.
[2]R. Swords, D. Mahalingam, M. O’Dwyer, C. Santocanale, K. Kelly, J. Carew, and F. Giles, Eur. J. Cancer, vol. 46, no. 1, pp. 33–40, Jan. 2010.
[3]A. Montagnoli, et al. Nat. Chem. Biol., vol. 4, no. 6, pp. 357–65, Jun. 2008.
[4]A. Montagnoli, P. Tenca, F. Sola, D. Carpani, D. Brotherton, C. Albanese, and C. Santocanale, Cancer Res, vol. 64, pp. 7110–7116, 2004.
[5]S. Rodriguez-Acebes, I. Proctor, M. Loddo, A. Wollenschlaeger, M. Rashid, M. Falzon, a T. Prevost, R. Sainsbury, K. Stoeber, and G. H.
Williams, Am. J. Pathol., vol. 177, no. 4, pp. 2034–45, Oct. 2010.
[6]E. S. Koltun, A. L. et al., Bioorg. Med. Chem. Lett., vol. 22, no. 11, pp. 3727–31, Jun. 2012.
[7]N. K. Sasi, K. Tiwari, F.-F. Soon, D. Bonte, T. Wang, K. Melcher, H. E. Xu, and M. Weinreich, PLoS One, vol. 9, no. 11, p. e113300, Jan. 2014.
Acknowledgements
This work was performed with the support of Wu K., McGarry E., O’Connor A., Natoni A., Barkley LR., and other
members in Corrado's lab, CCB and NCBES. This work was funded by Molecular Medicine Ireland as part of the
Clinical & Translational Research Scholars Programme.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
PREVALENCE OF PSEUDOTROMBOCYTOPENIA IN PATIENTS WITH HEPATOSPLENIC
SCHISTOSOMIASIS MANSONI
Author(s) and
Affiliation(s)
Guilherme Vaz de Melo Trindade ;Thiago de Almeida Pereira ; Amir Shaffat ; José Roberto Lambertucci
1. Department of Physiology, Schoool of Medicine, National University of Ireland Galway;
2. Departamento de Clínica Médica, Infectologia e Medicina Tropical , Faculdade de Medicina,
Universidade Federal de Minas Gerais
ABSTRACT
Pseudothompocytopenia (PTP) is a technical artifact generated by pre analytical errors
which affects the sample quality used in automated analytical processes. The PTP is due to
antigenic exposure of glycoprotein IIb/IIIa to ethylene-dinitro-tetraacetic acid (EDTA).
Patients with normal platelet counts and pseudotromboctopenia may be subject to
iatrogenic therapeutic and diagnostic invastigation, such as, corticosteroids therapy, bone
marrow puncture and platelet concentrate transfusion or esplenectomy. Presently these
patients often don’t receive adequate surgical treatment because surgeons are not aware of
the presence of a false low platelet count (or Pseudotrombocytopenia). Patients with
hepatosplenic form of schistosomiasis (HSS) can not be subject to invasive procedures that
in many cases would be the best treatment option, because they have low platelet count
which may not correspond to reality. Objective: To determine the prevalence of PTP in
patients with HSS. Patients and Methods: To investigate PTP prevalence in this group of
patients we performed a clinical-laboratory cross sectional study examining blood samples
of patients with HSS and controls. We selected 136 volunteers, being 67 with HSS and 67
without the disease. The test consisted in platelet counting using Fonio indirect method in
anticoagulant-free sample and automated platelet count usisng EDTA as anticoagulant in
whole blood sample at times 20 and 180 minutes, and simultaneously performing the above
procedure by changing the anticoagulant to sodium citrate. Results: We found platelet
clumps in 7.5% of HSS patients and 0% in controls without HSS. Contrary to what the clinical
and laboratory pratice suggests, PTP prevalence in anticoagulated samples with sodium
citrate was 19.4% in HSS patients and 9.0 % in the group without HSS. Conclusion: The
prevalence of PTP in patients with HSS was 7.5% with the use of EDTA and 19.4% with
sodium citrate.
Key words: Pre analytical erros, schitosomiasis, platelet, Pseudotrombocytopenia
References
1. Drummond S.C., Pereira P.N., Otoni A., Chaves B.A,. Antunes C.M., Lambertucci J.R.
Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for
Schistosomiasis mansoni. Rev. Soc. Bras. Med. Trop. 2014 Mar-Apr; 47(2):218-22.
2. Cohen A.M., Cycowitz Z., Mittelman M., Lewinski U.H, Gardyn J. The incidence of
pseudothrombocytopenia in automatic blood analyzers. Haematologia (Budap). 2000;30(2):117-21.
Acknowledgements
This study was supported by funding from CAPES fellowship from the Brazilian government.
1,2
2
1
2
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
ABSTRACT TITLE
IDENTIFICATION OF TRIPLE NEGATIVE BREAST CANCER (TNBC) SUBTYPES BY AN
IMMUNOHISTOCHEMISTRY (IHC) PANEL WITH IMPACT ON CLINICAL OUTCOMES
1
Author(s) and
Affiliation(s)
ABSTRACT
References
Acknowledgement
s
2
2
2
3
2
2
E.M. Walsh , A. Shalaby , L.S. Murillo , M.J. Webber , M.J. Kerin , S.A. Glynn , G.M. Callagy , H.
2
1
Ingoldsby , M.M. Keane
1
Department of Medical Oncology, Galway University Hospital;
2
Discipline of Pathology, School of Medicine, National University of Ireland, Galway;
3
Discipline of Surgery, School of Medicine, National University of Ireland, Galway
Background TNBC comprises 10-20% of breast cancers. Lehman et al identified 6 subtypes of
TNBC by gene expression profiling: BL1, BL2, IM, M, MSL & LAR. Despite the heterogeneity of
TNBC, standard of care is combination chemotherapy as in non TNBC subtypes. Identification of
TNBC subtypes responsive to various chemotherapies is necessary. In chemoresistant TNBC,
alternative therapeutic targets will facilitate improved treatment strategies.
Aims: 1. To validate a biomarker panel to define molecular subtypes of TNBC by IHC. 2. To correlate
molecular subtypes with prognosis to identify appropriate treatment regimens. 3. To improve
diagnostic and prognostic tools to individualize therapeutic strategies based on specific TNBC
subtypes
Methods A tissue microarray (TMA) was constructed of 197 TNBCs diagnosed from 1999 – 2014.
An 8-protein IHC panel was developed to identify TNBC subtypes on FFPE tissue. The panel
includes markers for key pathways to discriminate between the 6 subtypes: AR, Bcl2, c -myc, TIE1,
PDGFC, MMP2, Il2R, MSH2. To date, AR & Bcl2 have been evaluated, toge ther with p53 & Ki67.
Cells staining with each antibody were assessed; 10% was used as the cut off for positivity. Clinical
data including demographics and treatment regimens were obtained from hospital records and
incorporated into the database with pathological and outcome data.
Results: Detailed results will be presented in table format. Observations from the data
AR positive TNBCs: Diagnosed at older age than other TNBC subgroups
Less likely to have BRCA mutations
More likely to be metastatic at diagnosis
Associated with longer median OS
21% of AR positive cases also Bcl2 positive
45% of AR positive cases had Ki67 <10%
Bcl2 positive TNBCs: Low rates of metastatic disease at diagnosis
Longest median time to progression
TNBCs with high Ki67: Shortest median overall survival
TNBCs with p53 mutation: 64% of p53 positive TNBCs had Ki67>10%
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This study was supported by funding from a National Breast Cancer Research Institute (NBCRI) Scholarship and a NUI Galway
School of Medicine Scholarship.
College of Medicine, Nursing & Health Sciences
Postgraduate Research Day 2015
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