“Everyone should do research”




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Finally, this presentation proposes a business model for managing and commercialising intellectual property within a public research hospital setting.




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A
SESSION 3: Chair Professor Paul Gatenby

12



Upstream Signalling to, and Negative Regulation of, Nod2


1,2,3Peter C Tyrer, 1Anna C Powell, 1EG Bean, 1Jennifer L Kerrigan, 2AR Foxwell, 1,3P Pavli.


1 Macrophage Biology Research Group, The Canberra Hospital, ACT 2606.

2 Faculty of Science, The University of Canberra, Bruce, ACT 2601.

3 Gastroenterology and Hepatology Unit, TCH, ACT 2606

peter.tyrer@act.gov.au


Introduction

Nod2 is predominantly expressed in monocytes and is a cytoplasmic sensor of the bacterial cell wall breakdown product, muramyl dipeptide (MDP). Mutations in Nod2 were the first genetic abnormalities implicated in Crohn’s disease. Aims: (i) To determine the relationship between Nod2 and the cell-surface receptor cC1qR (cell-surface calreticulin) and (ii) to understand the regulation of Nod2 by the anti-inflammatory cytokine, transforming growth factor (TGF)-.


Methods

THP-1 human monocyte-derived cells were stimulated using lipopolysaccharide (LPS) or MDP; MDP/cC1qR interactions were determined by widefield deconvolution immunofluorescence (IF) microscopy followed by image analysis. These studies were complemented by immunoprecipitation (IP) studies. The effect of TGF- on Nod2 signalling was assessed by stimulating THP-1 cells using LPS, MDP, both LPS & MDP with or without TGF- exposure. Image analyses of IF results were used to determine the degree of NF-B translocation into the nucleus (downstream effect of Nod2 activation). Image analysis of stimulated peripheral blood monocytes was used to examine the interactions between Nod2 and TGF- signal transduction components.


Results

IF microscopy demonstrated that cC1qR and Nod2 interacted at the plasma membrane of THP-1 cells; this interaction was confirmed by IP. TGF- inhibited Nod2- and LPS-induced NF-B activation. MDP & LPS combined prevented NF-B nuclear translocation. TGF- signalling components were shown to colocalise with Nod2 in primary human monocytes.


Conclusion

These data support the hypothesis that Nod2 sensing of MDP is mediated through cC1qR and that TGF- negatively regulates Nod2 signalling. Nod2 may be a negative regulator of LPS-induced signalling. To confirm the importance of the interaction between Nod2 and cC1qR, further studies will be undertaken using siRNA molecules.


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A13


TRENDS IN HIP FRACTURE (HF) EPIDEMIOLOGY IN THE NEW MILLENNIUM IN THE AUSTRALIAN CAPITAL TERRITORY (ACT)


1ED O’Brien, 1, 2AA Fisher

1 Department of Geriatric Medicine, The Canberra Hospital, Garran, 2605

2 The Australian National University Medical School, Canberra, 0200

email: eddied.o’brien@act.gov.au


Introduction

With the ageing of the population, a marked continuous increase in the number of HFs was predicted worldwide. It has been predicted that HFs would rise by 83.7% in the ACT from 1994 to 2011 (Fisher et al 2007). In 2000, anti-osteoporotic treatment with bisphosphonates was introduced. The objectives of this study were to analyse trends in sex- and age-specific rates of HF and the impact of bisphosphonate use.

Methods

We determined the annual incidence of HF per 100,000 population using The Canberra Hospital administrative databases for the 8-year period (July 1999 to June 2007) and population data from the Australian Bureau of Statistics. Prescribing data for bisphosphonates were obtained from the Commonwealth Department of Health and Ageing.

Results

Of 1397 cases of HF (68.6% female) recorded in the 8-year period, 1252 (89.6%) were in persons aged 60 years and over and 1036 (74.2%) in persons 75 years and over. Compared with the earlier observations, the average number of HF per year in persons ≥ 60 years increased from 130.8 to 156.5 (19.6%), but the rate decreased by 4.8% from 403.4 to 384.0 per 100,000. Most decrease was caused by a 24.1% fall in the rate in females ≥ 60 years (from 552.1 in 1999/2000 to 419.2 in 2006/7) after the antiresorptive therapy was introduced. The number of prescriptions for bisphosphonates dispensed in the ACT increased from 245 to 51,271 in this period.


Conclusion

Hip fracture continues to be a major problem, although the earlier predicted rising trend has reversed for women, but not for men, coincident with an increased prescribing of bisphosphonates. As this is an ecologic study, caution should be used in attributing causation.


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A14


ANTIBIOTIC RESISTANCE OF PROPOBIONIBACTERIUM ACNES IN GENERAL PRACTICE PATIENTS WITH ACNE.


1H Toyne, 2C Webber, 1K Dwan, 3P Collignon, 1M Kljakovic


1School of General Practice, Rural, and Indigenous Health, Australian National University Medical School, Canberra 0200 2General Practitioner, Manuka ACT 2603, 3Infectious Diseases and Microbiology Department, Canberra Hospital and the Australian National University Medical School, Canberra 0200

helen.toyne@anu.edu.au


Introduction

There has been concern about the possible adverse physical affects in the long term use of antibiotics to manage acne. In this study we measured the carriage rate of p.acnes in acne patients presenting to Canberra General Practitioners (GPs) and calculated the rate of resistance to commonly used antibiotics. We then compared this to a similar study conducted in 1998. We also evaluated a number of factors which could influence the carriage of resistant organisms, and the past and current acne treatments used by patients presenting in general practice.


Methods

GPs who are members of PracNet (ACT and Southern NSW general practice research network) swabbed the skin of sequential patients aged 14-40 with acne who presented for any reason. GPs completed a questionnaire designed to detect factors possibly associated with antibiotic resistance.


Results

94/116 (81%) of patients had p.acnes isolated from their skin in the current study compared with 86/99 (87%) of patients in the 1998 study (p=0.172). 8/94 (9%) of patients in 2007 and 4/86 (5%) of patients in 1998 grew p.acnes resistant to at least one antibiotic (p=0.59). The only factor significantly associated with carriage of a resistant organism was current use of an antibiotic (OR 16.9, p=.001). There was less use of antibiotics for acne by patients in the current study (16%) compared to those in the 1998 study (36%).


Conclusion

The rate of p.acnes resistance has not changed significantly over this 10 year period. Current use of an antibiotic markedly increases the chance of carrying a resistant organism. There appears to be a decrease in the frequency of antibiotic use for acne in general practice patients.


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A15

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