Medicine and Health Sciences Commons^™

Lipid Anti-Lipid Antibody Responses Correlate With Disease Activity In Systemic Lupus Erythematosus, Vojislav Jovanovic, Nurhuda Abdul Aziz, Yan Ting Lim, Amanda Ng Ai Poh, Sherlynn Jin Hui Chan, Eliza Ho Xin Pei, Fei Chuin Lew, Guanghou Shui, Andrew M. Jenner, Li Bowen, Eoin F. Mckinney, Paul A. Lyons, Michael D. Kemeny, Kenneth G.C. Smith, Markus R. Wenk, Paul A. Macary

Illawarra Health and Medical Research Institute

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using …

Neurotrophin Signaling And Alzheimer's Disease Neurodegeneration - Focus On Bdnf/Trkb Signaling, Jenny Wong

Illawarra Health and Medical Research Institute

Neurotrophins are small proteins vital for neuronal growth, differentiation, survival, and plasticity. Members of the mammalian neurotrophin family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin- 4/5 (NT-4/5). Their neurotrophic effects are mediated by the tropomyosin receptor kinase (Trk) receptors, membrane-bound receptor tyrosine kinases (NGF for TrkA, BDNF and NT4/5 for TrkB, and NT-3 for TrkC) which activate various cell signaling pathways linked to growth, differentiation, and survival. The importance of neurotrophin signaling in brain development is highlighted by findings showing that knockout mice for any one of the neurotrophins or their receptors are fatal …

Increased Apolipoprotein D Dimer Formation In Alzheimer's Disease Hippocampus Is Associated With Lipid Conjugated Diene Levels, Surabhi Bhatia, Andrew M. Jenner, Hongyun Li, Kalani Ruberu, Adena S. Spiro, Claire E. Shepherd, Jillian J. Kril, Nupur Kain, Anthony Don, Brett Garner

Illawarra Health and Medical Research Institute

Previous studies indicate that apolipoprotein D (apoD) may have a lipid antioxidant function in the brain. We have shown that apoD can reduce free radical-generating lipid hydroperoxides to inert lipid hydroxides in a reaction that involves conversion of surface exposed apoD methione-93 (Met93) residue to Met93-sulfoxide (Met93-SO). One consequence of this reaction is the formation of a stable dimerized form of apoD. As cerebral lipid peroxidation is associated with Alzheimer's disease (AD), in the present study we aimed to assess the possible presence of apoD dimers in postmortem hippocampal and cerebellar tissues derived from a cohort of pathologically defined cases …

Mouse Strain-Dependent Variation In Obesity And Glucose Homeostasis In Response To High-Fat Feeding, M K. Montgomery, N L. Hallahan, S H. Brown, M Liu, T W. Mitchell, G J. Cooney, N Turner

Illawarra Health and Medical Research Institute

Aims/hypothesis: Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated strain-dependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N). Methods: Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to …

Structural And Functional Aspects Of Hetero-Oligomers Formed By The Small Heat Shock Proteins Αb-Crystallin And Hsp27, J Andrew Aquilina, Sudichhya Shrestha, Amie M. Morris, Heath Ecroyd

Illawarra Health and Medical Research Institute

Small heat shock proteins (sHSPs) exist as large polydisperse species in which there is constant dynamic subunit exchange between oligomeric and dissociated forms. Their primary role in vivo is to bind destabilized proteins and prevent their misfolding and aggregation. αB-Crystallin (αB) and HSP27 are the two most widely distributed and most studied sHSPs in the human body. They are coexpressed in different tissues, where they are known to associate with each other to form hetero-oligomeric complexes. In this study, we aimed to determine how these two sHSPs interact to form hetero-oligomers in vitro and whether, by doing so, there is …

Dha Prevents Altered 5-Ht1a, 5-Ht2a, Cb1 And Gabaa Receptor Binding Densities In The Brain Of Male Rats Fed A High-Saturated-Fat Diet, Yinghua Yu, Yizhen Wu, Craig Patch, Zhixiang Wu, Alexander Szabo, Duo Li, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Low levels of docosahexaenoic acid (DHA) have been linked to a number of mental illnesses such as memory loss, depression and schizophrenia. While supplementation of DHA is beneficial in improving memory and cognition, the influence of dietary fats on the neurotransmitters and receptors involved in cognitive function is still not known. The aim of this study was to investigate serotonin receptor (5-HT_1A and 5-HT_2A), cannabinoid receptor (CB1) and gamma-aminobutyric acid type A (GABA_A) receptor binding densities in the brain of male rats fed a high-saturated-fat (HF) diet, as well as the effect of DHA supplementation …

Cognitive, Affective And Social Processes Involved In Help-Negation After Critical Suicidal Thoughts, Coralie Wilson, Alexander Svenson, Peter Caputi

Illawarra Health and Medical Research Institute

Presentation at the National Suicide Prevention Conference, Melbourne Australia, July 2013

Help-negation is defined as the process of help withdrawal or avoidance found among those currently experiencing clinical and subclinical levels of different forms of psychological distress, including low and critical levels of suicidal ideation (Wilson, Bushnell, Caputi, 2011). Understanding the determinants of help-negation in suicidal samples that have not yet come to treatment provides a potent opportunity to target prevention and early intervention strategies to facilitate appropriate and timely help-seeking. Over 20 help-negation studies have ruled out variables that might explain the withdrawal process associated with suicidal thoughts. These …

Preventing Help-Negation For Suicidal Ideation: Implications For Thwarted Belongingness, Social Network Size And Frequency Of Social Interaction, Alexander Svenson, Coralie J. Wilson, Peter Caputi

Illawarra Health and Medical Research Institute

Poster presented at the National Suicide Prevention Conference, Melbourne Australia, July 2013

Help-negation is seen when the severity of an individual's suicidal ideation increases and they become less likely to seek help as a result of their condition. Research has implicated distorted affect regulation and perceptual processes related to social support in the development of help-negation among suicidal individuals (Wilson et al., 2013). Future research needs to focus on psycho-social factors that can be linked to neurological processes that differentiate suicidal individuals from controls and are directly implicated in the help-negation processes associated with suicidal ideation. As suicidal individuals have …

Reciprocity As Deliberative Capacity: Lessons From A Citizens Deliberation On Carbon Pricing Mechanisms In Australia, Alex Y. Lo, Kim S. Alexander, Wendy Proctor, Anthony Ryan

Illawarra Health and Medical Research Institute

Australia has seen a deep division in opinion in search of a carbon pricing mechanism. While concepts of carbon taxation and emission trading have comparable public support, climate scepticism is influencing the debates in political and public spheres in downplaying the need for carbon pricing. Public deliberation is a possible engagement option to address the conflict inherent in climate policy preferences. This research explores the way that a deliberative forum involving twenty-four Australians promoted effective communication between participants through which conflict between policy preferences became more tangible. While the forum did not eliminate disagreement in preferences in the choice of …

Recent Highlights In The Development Of Isatin-Based Anticancer Agents, Kara L. Vine, Lidia Matesic, Julie M. Locke, Danielle Skropeta

Illawarra Health and Medical Research Institute

Isatin (1H-indole-2,3-dione) and its derivatives are responsible for a broad spectrum of biological activities. Among these the cytotoxic and antineoplastic properties have been the most widely reported. The synthetic versatility of the isatin, due to its privileged scaffold, has led to the generation of a large number of structurally diverse derivatives which include analogues derived from either mono-, di-, and trisubstitution of the aryl ring A, and/or those obtained by derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. These compounds inhibit cancer cell proliferation and tumour growth via interaction with a variety of intracellular targets such as DNA, telomerase, …

Men Who Have Sex With Men, Infectious Syphilis And Hiv Coinfection In Inner Sydney: Results Of Enhanced Surveillance, Susan J. Botham, Kelly-Anne Ressler, Patrick Maywood, Kirsty G. Hope, Chris P. Bourne, Stephen J. Conaty, Mark J. Ferson, Darren J. Mayne

Illawarra Health and Medical Research Institute

Background: The resurgence of infectious syphilis in men who have sex with men (MSM) has been documented worldwide; however, HIV coinfection and syphilis reinfections in MSM in inner Sydney have not been published.

Methods: For all laboratory syphilis notifications assessed as a newly notified case or reinfection, a questionnaire was sent to the requesting physician seeking demographic data and disease classification. Sex of partner and HIV status were collected for all infectious syphilis notifications in men received from 1 April 2006 to March 2011.

Results: From April 2001 to March 2011, 3664 new notifications were received, 2278 (62%) were classified …

Pregnancies Following The Use Of Balloon Tamponade Technology In The Previous Pregnancy, C Georgiou

Illawarra Health and Medical Research Institute

Abstract of an E-posters that presented at the RCOG World Congress 2013, 24-26 June 2013, Liverpool, United Kingdom.

Teasaponin Reduces Inflammation And Central Leptin Resistance In Diet-Induced Obese Male Mice, Yinghua Yu, Yizhen Wu, Alexander Szabo, Zhixiang Wu, Hongqin Wang, Duo Li, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Chronic inflammation is involved in the pathogenesis of obesity and type 2 diabetes. Recently, teasaponin, an extract from tea, has been shown to have anti-inflammatory effects. We examined the effect of teasaponin on obesity, inflammation, glucose metabolism and central leptin sensitivity, in obese mice fed a high-fat (HF) diet for 16 weeks. Intraperitoneal injections of teasaponin (10mg/kg, daily) for 21 days significantly decreased the food intake and body weight of HF diet-induced obese mice. Teasaponin treatment also reduced the protein levels of pro-inflammatory cytokines (TNF-α, IL-6 and/or IL-1β) and NF-κB signaling (p-IKK and p-IκBα) in adipose tissue and the liver. …

Effects Of Antipsychotic Medications On Appetite, Weight, And Insulin Resistance, Chao Deng

Illawarra Health and Medical Research Institute

Although clozapine, olanzapine, and other atypical antipsychotic drugs (APDs) have fewer extrapyramidal side effects, they have serious metabolic side effects such as substantial weight gain, intra-abdominal obesity, and type 2 diabetes mellitus. Given that most patients with mental disorders face chronic, even life-long, treatment with APDs, the risks of weight gain/obesity and other metabolic symptoms are major considerations for APD maintenance treatment. This review focuses on the effects of APDs on weight gain, appetite, insulin resistance, and glucose dysregulation, and the relevant underlying mechanisms that may be help to prevent and treat metabolic side effects caused by APD therapy.

Cerium Oxide Nanoparticles: Influence Of The High-Z Component Revealed On Radioresistant 9l Cell Survival Under X-Ray Irradiation, Adam Briggs, Stephanie Corde, Sianne Oktaria, Ryan Brown, Anatoly B. Rosenfeld, Michael Lerch, Konstantin Konstantinov, Moeava Tehei

Illawarra Health and Medical Research Institute

This article pioneers a study into the influence of the high-Z component of nanoparticles on the efficacy of radioprotection some nanoparticles offer to exposed cells irradiated with X-rays. We reveal a significant decrease in the radioprotection efficacy for cells exposed to CeO2 nanoparticles and irradiated with 10 MV and 150 kVp X-rays. In addition, analysis of the 150 kVp survival curve data indicates a change in radiation quality, becoming more lethal for irradiated cells exposed to CeO2 nanoparticles. We attribute the change in efficacy to an increase in high linear energy transfer Auger electron production at 150 kVp which counterbalances …

Laparoscopic Management Of An Adnexal Mass During The Second Trimester Of Pregnancy, C Georgiou

Illawarra Health and Medical Research Institute

Abstract of paper presented at AGES XXIII Annual Scientific Meeting, Brisbane, 2013.

Thrombus-Like Structures Seen In The Infundibular-Pelvic Ligament During The Laparoscopic Management Of Ovarian Torsion, C Georgiou

Illawarra Health and Medical Research Institute

Abstract of paper presented at AGES XXIII Annual Scientific Meeting, Brisbane, 2013.

Benefits, Issues, And Recommendations For Personalized Medicine In Oncology In Canada, C Butts, S Kamel-Reid, G Batist, S Chia, C Blanke, M Moore, M B. Sawyer, C Desjardins, A Dubois, J Pun, K Bonter, F D. Ashbury

Illawarra Health and Medical Research Institute

The burden of cancer for Canadian citizens and society is large. New technologies have the potential to increase the use of genetic information in clinical decision-making, furthering prevention, surveillance, and safer, more effective drug therapies for cancer patients. Personalized medicine can have different meanings to different people. The context for personalized medicine in the present paper is genetic testing, which offers the promise of refining treatment decisions for those diagnosed with chronic and life-threatening illnesses. Personalized medicine and genetic characterization of tumours can also give direction to the development of novel drugs. Genetic testing will increasingly become an essential part …

Proenergetic Effects Of Resveratrol In The Murine Neuronal Cell Line Neuro2a, Nhu T.Q Nguyen, Lezanne Ooi, Sabine C. Piller, Gerald Munch

Illawarra Health and Medical Research Institute

Scope: Energy deficit is a common characteristic of neurodegenerative disorders, including Alzheimer's disease. Adenosine monophosphate activated protein kinase (AMPK) is a key enzyme maintaining energy balance by regulating the cellular uptake of glucose, β-oxidation of fatty acids, and expression of glucose transporter 4. Since resveratrol has been shown to increase the activity of AMPK, we hypothesized that it might influence energy metabolism in a model neuron-like cell line, murine Neuro2a cells.

Methods and results: Resveratrol caused an elevation of adenosine triphosphate (ATP) and guanosine triphosphate (GTP) in a dose-dependent manner. The highest ATP and GTP levels achieved by treatment with …

The Key Regulatory Roles Of The Pi3k/Akt Signaling Pathway In The Functionalities Of Mesenchymal Stem Cells And Applications In Tissue Regeneration, Jiezhong Chen, Ross Crawford, Chen Chen, Yin Xiao

Illawarra Health and Medical Research Institute

Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types and have been widely used in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity …

High-Dose Mushroom Increases Hepatic Accumulation Of Triacylglycerol In Rats Fed With High-Fat Diet, D Handayani, B Meyer, J Chen, S Brown, T Mitchell, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Abstract of poster that presented at IUNS 20th International congress of Nutrition, Granada, Spain, September 15-20, 2013.

Author Reply, John Carmody, Victoria Traynor, Don C. Iverson, Elena M. Marchetti

Illawarra Health and Medical Research Institute

We thank Regal[1] for his interest and his kind comments regarding our paper.[2] Our principal aim was to highlight several key ethical issues faced by Australian physicians (e.g. reporting obligations, negative consequences of driving cessation). Regal raises a challenging, yet unresolved, dilemma: which test best determines safe driving capacity? Although an in-depth appraisal of existing tests was beyond the scope of our paper, we did refer to two seminal reviews. The Australian and New Zealand Society of Geriatric Medicine (ANZSGM)[3] and the American Academy of Neurology (AAN)[4] have comprehensively reviewed the existing literature regarding assessment of fitness to drive of …

An Objective Index Of Walkability For Research And Planning In The Sydney Metropolitan Region Of New South Wales, Australia: An Ecological Study, Darren J. Mayne, Geoffrey Morgan, Alan Willmore, Nectarios Rose, Bin Jalaludin, Hilary Bambrick, Adrian Bauman

Illawarra Health and Medical Research Institute

Background: Walkability describes the capacity of the built environment to support walking for various purposes. This paper describes the construction and validation of two objective walkability indexes for Sydney, Australia.

Methods: Walkability indexes using residential density, intersection density, land use mix, with and without retail floor area ratio were calculated for 5,858 Sydney Census Collection Districts in a geographical information system. Associations between variables were evaluated using Spearman’s rho (ρ). Internal consistency and factor structure of indexes were estimated with Cronbach’s alpha and principal components analysis; convergent and predictive validity were measured using weighted kappa (κw) and by comparison with …

In Vivo Pharmacological Evaluations Of Novel Olanzapine Analogues In Rats: A Potential New Avenue For The Treatment Of Schizophrenia, Somayeh Jafari, Xu-Feng Huang, Jessica L. Andrews, Francesca Fernandez-Enright

Illawarra Health and Medical Research Institute

Olanzapine (Olz) is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4′-methylpiperazin-1′-yl)-10Hbenzo[b]thieno[2,3-e][1,4]diazepine), and OlzHomo (2-ethyl-4-(4′-methyl-1′,4′-diazepan-1′-yl)-10H-benzo[b]thieno[2,3-e] [1,4]diazepine), for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally …

Novel Implications Of Lingo-1 And Its Signalling Partners In The Dorsolateral Prefrontal Cortex In Schizophrenia, Jessica L. Andrews, Kelly A. Newell, Xu-Feng Huang, Francesca Fernandez-Enright

Illawarra Health and Medical Research Institute

No abstract provided.

Analysis Of The Psychological Impact Of A Vascular Risk Factor Intervention: Results From A Cluster Randomized Controlled Trial In Australian General Practice, Suzanne Helen Mckenzie, Upali W. Jayasinghe, Mahnaz Fanaian, Megan Passey, Mark Fort Harris

Illawarra Health and Medical Research Institute

Background Screening for vascular disease, risk assessment and management are encouraged in general practice however there is limited evidence about the emotional impact on patients. The Health Improvement and Prevention Study evaluated the impact of a general practice-based vascular risk factor intervention on behavioural and physiological risk factors in 30 Australian practices. The primary aim of this analysis is to investigate the psychological impact of participating in the intervention arm of the trial. The secondary aim is to identify the mediating effects of changes in behavioural risk factors or BMI. Methods This study is an analysis of a secondary outcome …

Sleep-Wake Behaviour And The Eeg In Altered States Of Consciousness, Sarah P. Loughran, Sabine Regel, Lilith Buetler, Martin Wieser, Robert Riener, Peter Achermann

Illawarra Health and Medical Research Institute

Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australia.

Central Administration Of Palmitic Acid Increases Food Intake And Body Temperature In Male Sprague Dawley Rats, Chi H. L Dinh, Alexander M. Szabo, Hongqin Wang, Yinghua Yu, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Abstract of a poster presentation at the World Diabetes Congress 2013

Characterization Of Forebrain Neurons Derived From Late-Onset Huntington's Disease Human Embryonic Stem Cell Lines, Jonathan C. Niclis, Anita Pinar, John M. Haynes, Walaa Alsanie, Robert Jenny, Mirella Dottori, David S. Cram

Illawarra Health and Medical Research Institute

Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin (HTT) gene. Recently, induced pluripotent stem cell (iPSC) lines carrying atypical and aggressive (CAG60+) HD variants have been generated and exhibit disparate molecular pathologies. Here we investigate two human embryonic stem ce ll (hESC) lines carrying CAG₃₇ and CAG₅₁ typical late-onset repeat expansions in comparison to wildtype control lines during undifferentiated states and throughout forebrain neuronal differentiation. Pluripotent HD lines demonstrate growth, viability, pluripotent gene expression, mitochondrial activity and forebrain specification that is indistinguishable from control lines. Expression …

An Improved High-Throughput Lipid Extraction Method For The Analysis Of Human Brain Lipids, Sarah K. Abbott, Andrew M. Jenner, Todd W. Mitchell, Simon H. Brown, Glenda M. Halliday, Brett Garner

Illawarra Health and Medical Research Institute

We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass-glass homogenization) was compared to a high-throughput method combining methyl-tert-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass-glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, …