Preventing the development of multi-organ autoimmunity

By Dr Jodie Abramovitch

Autoimmune disease occurs when the immune system incorrectly recognises self-tissues and organs as being potentially dangerous - like a pathogen. The immune system attacks the tissue or organ – sometimes in an organ-specific manner (eg. type I diabetes) or sometimes in a multi-organ fashion (eg. lupus) – which leads to disease symptoms. What causes the onset of autoimmune disease is not well understood and, consequently, there is no cure with treatments predominantly aimed at relieving inflammatory symptoms.

Elisha de Valle - first author of this study

In a collaborative study, Monash researchers examined the role of transcription factor NF-κB1 in a specific type of immune cell, Follicular B cells (Fo B cells), and its role in controlling multi-organ autoimmune disease. NF-κB1 is important for regulating B cell function and when Fo B cells become deregulated they can produce antibodies that target and destroy vital organs. The authors of this study used a mouse model that lacks the NF-κB1 gene and analysed the effect on Fo B cells. They found that Fo B cells lacking NF-κB1 secreted a large amount of pro-inflammatory factor IL-6 and this had an effect on surrounding immune cells. Specifically, IL-6 led to the over stimulation of B cells which resulted in the formation of  germinal centre structures (sites where antibody responses are launched) and, in turn, an increase in the presence of self-reacting antibodies against self-tissues and organs within the NF-κB1 deficient mice. Moreover, IL-6 also caused Fo B cells to proliferate at a higher rate which exacerbated the germinal centre B cell response. Without NF-κB1, the mice developed severe multi-organ autoimmune disease and had a reduced life span compared to healthy mice. This was largely attributable to the production of IL-6 by Fo B cells. Importantly, when IL-6 was blocked the development of autoimmune disease was greatly reduced.

This study revealed that NF-κB1 has an essential role in controlling the function of Fo B cells, primarily to limit the production of inflammatory factor IL-6. In the absence of NF-κB1, the production of IL-6 becomes deregulated and severe autoimmune disease can occur. These conclusions further the understanding of the mechanisms that control IL-6 production and may lead to better management of patients with autoimmune disease.

Reference: de Valle E, Grigoriadis G, O'Reilly LA, Willis SN, Maxwell MJ, Corcoran LM, Tsantikos E, Cornish JK, Fairfax KA, Vasanthakumar A, Febbraio MA, Hibbs ML, Pellegrini M, Banerjee A, Hodgkin PD, Kallies A, Mackay F, Strasser A, Gerondakis S, Gugasyan R. NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med. 2016 Apr; 213:621-41. 

doi: 10.1084/jem.20151182.

Which type of polio vaccine is best?

By Dr Jodie Abramovitch

The current polio vaccine was developed by Albert Sabin in 1961 and is a live-attenuated, orally administered vaccine (OPV). Live-attenuated means that the polio virus is alive but unable to cause disease. In settings with high childhood mortality, the OPV is believed to have non-specific effects that allows for protection against other childhood infections such as paralytic poliomyelitis (also known as infantile paralysis caused by the polio virus), tuberculosis and measles. This non-specific protection is thought to be able to reduce mortality to infectious diseases, particularly in childhood, by up to 17%. The significance of this protection is controversial.

Professor Magda Plebanski

To reduce the incidence of poliomyelitis which is around 75 cases worldwide per year, the World Health Organisation (WHO) has recommended the OPV be replaced by an inactivated form (IPV) of the polio virus. Inactivated means the virus used in the vaccine is dead.

In a recent correspondence published in The Lancet, a group of physicians and scientists, including Professor Magdalena Plebanski from the Department of Immunology and Pathology, voiced their concern at a potential change to the form of the current polio vaccine from OPV to IPV. It was noted that previous evidence suggests that the IPV does not confer the same non-specific protection as the OPV. Therefore, the IPV may be associated with an increase in childhood mortality (caused by a range of different infectious diseases). The authors postulated that for every case of poliomyelitis that is reduced by the IPV about 4000 extra deaths due to other infectious diseases (resulting in 300 000 additional deaths each year) may occur that could have been prevented by the OPV.

The authors of this correspondence concluded by urging the WHO to conduct randomised trials of the two different forms of polio vaccine before phasing out the OPV. This would allow for a better understanding of the non-specific protection that each of the polio vaccines provides against other infectious diseases. The results of these trials would inform whether the IPV leads to a higher infectious disease mortality overall when compared to the OPV, as well as whether the OPV and IPV may be administered alongside one another in children to prevent poliomyelitis and keep infectious disease mortality low.

Reference: Fish EN, Flanagan KL, Furman D, Klein SL, Kollmann TR, Jeppesen DL, Levy O, Marchant A, Namachivayam S, Netea MG, Plebanski M,Rowland-Jones SL, Selin LK, Shann F, Whittle HC.  Changing oral vaccine to inactivated polio vaccine might increase mortality. Lancet. 2016 Mar; 387:1054-5.
doi: 10.1016/S0140-6736(16)00661-9.

Recurrent bacterial vaginosis - a female perspective

By Dr Jodie Abramovitch

Dr Jade Bilardi - first author of the BV study

The most common vaginal infection of women of reproductive age is bacterial vaginosis (BV). BV is characterised by an imbalance of natural vaginal bacteria species leading to symptoms such as abnormal odour and discharge. It has more seriously been associated with an increased incidence of miscarriage, premature birth, HIV and a higher risk of acquiring a sexually transmitted infection.

The cause of BV and the way it is transmitted from person to person are not well understood. However, there is increasing evidence BV may be sexually transmitted. Current treatment and patient management is suboptimal, leading to a high recurrence rate among affected women.

Interactions of bacterial and fungal pathogens in humans

By Dr Jodie Abramovitch

Multi-drug resistant bacteria strains are becoming an increasingly serious problem within a clinical setting. One type of bacteria that can rapidly acquire antibiotic resistance and cause problems in humans is Acinetobacter baumannii. Often A. baumannii is found alongside the fungus Candida albicans which can cause yeast infections, especially within intensive care wards.

Professor Anton Peleg

Monash researchers led by Professor Anton Peleg from the Department of Infectious Diseases and Microbiology had previously noted that A. baumannii and C. albicans were able to inhibit each other’s growth under certain conditions. To explore this interaction further, this study sought to understand the molecular mechanisms behind the inhibition of growth of A. baumannii by C. albicans.

Farnesol is a compound secreted by C. albicans continuously during its growth. This compound was shown to be able to inhibit growth of A. baumannii. Farnesol, upon further investigation, was found to interfere with gene expression that was responsible for maintaining the cell membrane and controlling cell division of the bacterium. The ability of the bacteria to create a biofilm (many bacteria adhere to one another in a protective layer) and move were also greatly impaired by farsenol secreted by C. albicans. This means that the infectivity of A. baumannii was greatly reduced.

This study of bacterial-fungal interactions has increased the understanding of how C. albicans can inhibit the growth and viability of A. baumannii. As such, this study concluded that by understanding how pathogens can compete with one another may allow for the identification of novel antimicrobials for the treatment of problematic human pathogens.

Reference: Kostoulias X, Murray GL, Cerqueira GM, Kong JB, Bantun F, Mylonakis E, Khoo CA, Peleg AY. Impact of a Cross-Kingdom Signaling Molecule of Candida albicans on Acinetobacter baumannii Physiology. Antimicrob Agents Chemother. 2015 Oct; 60:161-7. 

doi: 10.1128/AAC.01540-15.

Is previous trauma adequately documented for female psychiatric inpatients?

By Dr Jodie Abramovitch 

Traumatic events can lead to long-lasting psychological changes in an affected person. Patients presenting with serious mental health issues are more likely to have experienced emotional or physical trauma in the past than healthy individuals.

Professor Jayashri Kulkarni - Director of MAPrc
and senior author of this study

Researchers from the Monash Alfred Psychiatry Research Centre (MAPrc) aimed to investigate the extent to which clinicians record previous trauma events. They then analysed this information to identify if it was incorporated into diagnosis and treatment of female psychiatric inpatients.

One hundred inpatients were selected for the study, with psychotic illnesses being the most prevalent primary diagnosis. For just over half these participants, there was no record of whether or not there was a history of trauma. Of the 49 patients asked about trauma history, 84% (41 patients) responded positively though only 3% of these documented cases had a specific description of the trauma. For 34 (of the 41 with trauma history) subjects, no mention was made of potentially trauma-associated psychiatric symptoms such as flashbacks or emotional numbing. This study also found that current drug use and/or a diagnosis of borderline personality disorder were associated with a higher likelihood of documented trauma.

As such, this study concluded that clinicians dealing with patients with mental illnesses need to be more proactive about documenting a comprehensive history of trauma to better inform patient management.

Reference: Xiao CL, Gavrilidis E, Lee S, Kulkarni J. Do mental health clinicians elicit a history of previous trauma in female psychiatric inpatients? J Ment Health. 2016 Feb (online)

doi:

10.3109/09638237.2016.1139074

Anti-AIDS drug can affect platelet activation

By Dr Jodie Abramovitch

Abacavir is an anti-retroviral medication that is commonly used to treat HIV infection to prevent or control the development of AIDS. Abacavir use has been associated with an increased risk for cardiovascular disease (CVD). However, it is unknown how abacavir leads to this increased risk of CVD.

Dr Janine Trevillyan - HIV researcher and
lead author of this study

Monash researchers from the Department of Infectious Diseases and the Australian Centre for Blood Diseases (ACBD) theorised that abacavir could be affecting platelet activation thus leading to the development of CVD. Therefore the aim of their study was to determine if platelet reactivity was altered with abacavir administration.

Patients with well controlled HIV infection on non-abacavir treatments were recruited from the Infectious Diseases clinic at the Alfred Hospital. Twenty selected patients were given abacavir alongside their non-abacavir treatments for 15 days and had blood samples taken at day 0, 15 (treatment ceased) and 28. Platelet reactivity (as measured by VASP-index) was significantly decreased during abacavir treatment (at day 15 compared to day 0). A measurable decrease in soluble glycoprotein VI levels (sGPVI) was also indicative of lower platelet reactivity. Platelet surface protein integrin-β3 was also observed to be lower which may suggest a change in platelet structure. At day 28 following clearance of abacavir from the body, measurements were similar to those taken at day 0.

The findings in this study show that abacavir does have an effect on platelet reactivity, though this is reversible following cessation of treatment. The link between platelets and CVD needs to be explored further and the clinical implications of these results requires more research in a larger group of patients. This study has identified possible markers of disease in sGPVI and integrin- β3.

Reference: Trevillyan JM, Arthur JF, Jing J, Andrews RK, Gardiner EE, Hoy JF. Effects of abacavir administration on structural and functional markers of platelet activation. AIDS. 2015 Nov: 29;2309-13. 

doi: 10.1097/QAD.0000000000000848

Identification of a mutation in red blood cells that can worsen sickle cell disease

By Dr Jodie Abramovitch

Sickle cell disease (SCD) is a genetic condition in which red blood cells (RBC) have an abnormal bowed or sickle shape due to a mutation of haemoglobin. These RBC are unable to travel well through small blood vessels, often becoming trapped and subsequently dying. This leads to a low red blood cell count (anaemia) which is why this disease can also be known as sickle cell anaemia. The trapped RBC can lead to occlusion of blood vessels leading to lack of oxygen and tissue death in many organ systems - producing extreme pain and organ failure.

L-R: Dr Fiona Brown, Prof. Stephen Jane,
Ms Loretta Cerruti, A/Prof David Curtis

RBC require electrolytes such as potassium (K) and chloride (Cl) to function properly. These electrolytes are actively moved in and out of cells by proteins called co-transporters. The K-Cl co-transporter, therefore, moves K and Cl along with water in and out of RBC to control cell size.

A recent study by researchers from the Australian Centre for Blood Diseases (ACBD), led by Associate Professor David Curtis and Professor Stephen Jane with collaborators from the Florey Institute and Walter and Eliza Hall Institute, identified a mutation within a K-Cl co-transporter known as Kcc1 in a mouse model. This mutation increased the activity of the K-Cl co-transporter leading to smaller RBC.

When the mutation in Kcc1 was introduced into a mouse model of SCD that mimics human disease, it was shown that disease was worsened. A higher proportion of RBC were sickle shaped which led to blocked small blood vessels and more extensive tissue damage. It was concluded that the mutation in Kcc1 was directly linked to a more serious presentation of SCD.

This research highlights the potential therapeutic use of targeting K-Cl (and other electrolyte) co-transporters to inhibit their activity in diseases such as SCD. 

Reference: Brown FC, Conway AJ, Cerruti L, Collinge JE, McLean C, Wiley JS, Kile BT, Jane SM, Curtis DJ. Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model. Blood. 2015 Dec:126;2863-70. 

doi: 10.1182/blood-2014-10-609362

Immune system 'patrolling' cells further understood

By Dr Jodie Abramovitch

Within the immune system there are patrolling cells that are constantly scanning the body for signs of infection. They are known as antigen presenting cells. Dendritic cells (DC) are the most efficient example of an antigen presenting cell. When DC find an infection, they are able to alert other cells of the immune system to attack and destroy the infection. Therefore the functions of DC are really important in an effective immune response.

Associate Professor Mark Wright, Head of
the Leucocyte Membrane Protein Group
and senior author of this study

Tetraspanins are a type of protein that are found at the cell surface. Here they bind and bring together (“organise”) other proteins and receptors at the cell surface. CD37 and CD82 are tetraspanins that allow DC to communicate with other immune cells that there is an infection present. CD37 is important for movement of DC to lymph nodes where they find other immune cells. The role of CD82 in DC migration is unclear.

In a recent study published by the Leucocyte Membrane Protein laboratory from the Department of Immunology and Pathology, in collaboration with Melbourne University and international colleagues, the roles of CD37 and CD82 in co-ordinating DC function in response to infection was assessed.

By studying activated DC, it was found that CD82 appeared to have an opposing function to CD37. Whereas CD37 expression was down-regulated following activation of DC, CD82 was up-regulated and restrained DC migration to lymph nodes. DC that were deficient in either CD37 or CD82 were unable to become fully functional and DC that were deficient in CD82 were able to spread much further than CD37 deficient DC. Thus, unactivated DC were observed to have high CD37 expression and low CD82 expression leading to a highly mobile cell that is able to travel easily around the body. Activated DC (DC that have sensed an infection) have low CD37 expression and high CD82 expression which limits mobility of the DC but is able to efficiently signal to immune cells that an infection is present.

This study has detailed a biology of DC that was not previously known and highlights the importance of tetraspanins in coordinating DC function. 

Reference: Jones EL, Wee JL, Demaria MC, Blakeley J, Ho PK, Vega-Ramos J, Villadangos JA, van Spriel AB, Hickey MJ, Hämmerling GJ, Wright MD. Dendritic Cell Migration and Antigen Presentation Are Coordinated by the Opposing Functions of the Tetraspanins CD82 and CD37. J Immunol. 2016 Feb: 196; 978-87. 

doi: 10.4049/jimmunol.1500357

A gluten-free diet improves symptoms of coeliac disease

By Dr Jodie Abramovitch

Coeliac disease is a condition in which the immune system launches an inflammatory response to gluten. In healthy individuals, this immune reaction does not occur. Due to the inflammatory response, patients with coeliac disease typically have damaged small intestines which can lead to malnutrition, weight loss and gastrointestinal symptoms such as nausea and bloating.

A gluten-free diet is ‘prescribed’ for patients with coeliac disease. Currently, prospective studies of the short and long term effects of a gluten-free diet on the symptoms and pathology of coeliac disease are lacking.

Professor Peter Gibson - Head of the Department
of Gastroenterology

Monash researchers from the Eastern Health Clinical School and supervised by Professor Peter Gibson from the Department of Gastroenterology at the Central Clinical School aimed to determine the time frame in which intestinal damage and associated nutritional deficiencies caused by coeliac disease were successfully treated.

Pitfalls of using mobile phone photos for the diagnosis of patients

By Dr Jodie Abramovitch

Smart (mobile) phones allow for rapid and multi-faceted communication between people. This feature of smart phones has been used with success within the clinic, allowing for real-time collaboration of doctors on specific cases when not everyone is present.

Medical student Jarrel Seah

However, as recently outlined in a short report lead authored by Monash University medical student Jarrel Seah, this useful technology has been shown to have a down side. A 45-year old woman was treated surgically for a brain aneurysm at the Alfred Hospital. A CT scan following the operation revealed the development of an area of the brain with poor blood flow.

The patient subsequently developed high intracranial (within the skull) pressure in the intensive care unit. This prompted another scan, and a mobile phone photo was taken of the computer screen upon which the scan was being viewed.

Returning to work after major trauma

By Dr Jodie Abramovitch

In high income countries, injury-related deaths have decreased between 1990 and 2013. This higher likelihood for survival following serious injury is attributed to effective prevention strategies and improved patient care. However there is still a limited understanding of the quality of patients’ recovery, how long recovery takes, and the proportion of injured patients who suffer lifelong disability.  

Professor Belinda Gabbe - Head of the Pre-Hospital,
Emergency and Trauma Research Unit in the
Department of Epidemiology and Preventive Medicine

The aim of a study conducted by Monash researchers from the Department of Epidemiology and Preventive Medicine (DEPM) and the Department of Surgery, alongside trauma services based at the Alfred hospital and collaborators from a number of different institutes, was to describe the long-term return to work and function of major trauma patients.

Adult major trauma survivors were assessed between 2007 and 2012 in Victoria at 6, 12 and 24 months after leaving hospital. Of the 8128 patients who were followed up, 23% had returned to their pre-injury condition by 24 months. Of those working or studying prior to injury, 70% had returned to work/study by 24 months. These outcomes were found to be influenced by multiple factors including age, socio-economic status and presence of pre-existing health conditions.

This study concluded that function and return to work improved with time following injury thus indicating that further improvements in health and quality of life may be expected after 24 months. However, ongoing disability was still prevalent at 24 months highlighting the need for future studies spanning longer than 24 months to fully assess the burden of major trauma on the lives of those affected.

The data collected in this study will assist with predicting the outcome of major trauma for individual patients and improve trauma services. This study also advocates for the improvement of rehabilitative and disability services to better the long-term health outcomes for patients.

Reference: Gabbe BJ, Simpson PM, Harrison JE, Lyons RA, Ameratunga S, Ponsford J, Fitzgerald M, Judson R, Collie A, Cameron PA. Return to Work and Functional Outcomes After Major Trauma: Who Recovers, When and How Well? Ann Surg. 2016 Jan.
doi: 10.1097/SLA.0000000000001564

Flu vaccine reduces risk of hospitalisation

By Dr Jodie Abramovitch

Professor Allen Cheng (left) and
Associate Professor Tom Kotsimbos (right)

Vaccination against influenza infection is recommended in high risk groups including the elderly, pregnant women and those with chronic illnesses. The flu vaccine is primarily aimed at reducing the severe health consequences of infection such as hospitalisation and death. However, most previous studies on the influenza vaccine were performed in healthy adults and have looked at protection against mild influenza infection rather than severe complications.

Predicting patients who require large blood transfusions

By Dr Jodie Abramovitch

Loss of large volumes of blood is responsible for a third of all deaths associated with trauma. The only way to treat a loss of blood, also known as haemorrhagic shock, is via transfusion of blood products. Some trauma patients require transfusion with incredibly large amounts of blood – a massive transfusion (MT) - and their survival may depend on the timely delivery of blood or blood products.  

Director of the National Trauma Research Institute
and senior author Professor Mark Fitzgerald

To create a robust system that allows for the prediction of patients who may require MT, researchers from Monash University and the Alfred Hospital (Trauma Centre, National Trauma Research Institute, Department of Epidemiology and Preventive Medicine and Ambulance Victoria) explored whether use of a ‘shock index’ (SI) calculated before and after arrival at hospital could predict MT. SI is calculated simply by measuring heart rate and dividing it by measured systolic blood pressure.

Of the 6990 major trauma patients who presented at the Alfred Hospital between 2006 - 2012, 5.2% (360 patients) received MT. By using a number of statistical models it was shown that a SI calculated before arrival at hospital was able to significantly improve prediction of MT. Combining the SIs calculated before and after arrival at hospital was only slightly better at predicting MT than the SI measured after arrival at hospital alone.

Considering these observations it was concluded that the SI is a simple option to assist with the prediction of MT. However further study is warranted to validate the SI prospectively. The development and implementation of computer-assisted data collection and prognostication may further enhance the utility of the SI in predicting MT.


Reference: Olaussen A, Peterson EL, Mitra B, O'Reilly G, Jennings PA, Fitzgerald M. Massive transfusion prediction with inclusion of the pre-hospital Shock Index. Injury  2015 May: 46;822-6. 
doi: 10.1016/j.injury.2014.12.009

Reducing cardiac fibrosis

By Dr Jodie Abramovitch

Cardiac fibrosis (scarring) causes the heart to become stiff which affects the ability of the heart to function normally. Cardiac fibrosis can lead to heart failure and is associated with a range of health problems including hypertension, diabetes and obesity.

Dr Anthony Dear

A new class of therapeutics used to treat diabetes, known as glucagon-like peptide-1 receptor (GLP-1R) agonists, help regulate glucose levels in the body. There is evidence that some GLP-1R agonists are able to improve vascular disease in mouse models.

Monash researchers from the Eastern Health Clinical School and the Department of Pharmacology, overseen by Dr Anthony Dear (also associated with the Australian Centre for Blood Diseases) have investigated the effect of a GLP-1R agonist on cardiac fibrosis in a number of different pathological settings.  The recently published work showed that mice with hypertension, obesity, or age induced cardiac fibrosis had reduced evidence of cardiac fibrosis following treatment with a GLP-1R agonist, regardless of diabetic status. Furthermore, reduced levels of inflammatory markers were found within the hearts of treated animals. This reduction in inflammation may be the mechanism behind the observed reduction in cardiac fibrosis.

These results show that GLP-1R agonists may have success in treating cardiac fibrosis, regardless of pathological cause (i.e. hypertension, obesity or age), in humans.

Reference: Gaspari T, Brdar M, Lee HW, Spizzo I, Hu Y, Widdop RE, Simpson RW, Dear AE. Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis. Diab Vasc Dis Res. 2016 Jan: 13;56-68.
doi: 10.1177/1479164115605000.

Anaphylaxis to oats – link between food-based moisturisers and food allergy

By Dr Jodie Abramovitch

Food allergy is a growing health issue and, for those affected, can be associated with serious medical outcomes. Allergic reactions to food can range from relatively mild (swelling, rashes) to potentially life threatening (anaphylaxis). 

Allergy Research Group:
(back) L-R Jade Jaffar, Nirupama Varese
Jennifer Rolland (Head), Robyn O'Hehir (Head), Jodie Abramovitch
(front) L-R Sara Prickett, Tracy Phan

Researchers within the Department of Allergy, Immunology and Respiratory Medicine (AIRMed) and the Department of Immunology and Pathology have recently published an interesting case study on oat allergy. A female patient presented with anaphylaxis following consumption of oats in an apple crumble crust. Analysis of the patient’s clinical history noted that, whilst previously able to eat oats without incident, she had been using an oat-based moisturiser to soothe her eczema (broken skin). The patient had also experienced some allergic symptoms (difficulty in breathing) in response to the moisturiser as well as an oat-based bath product.

Experiments were able to show that the patient had oat-specific IgE antibodies (a diagnostic marker of allergy) within her blood. In the presence of oat extract or the oat-containing products, these antibodies were able to activate the patient's basophils, an important cell type activated during an allergic reaction, indicating that they were indeed leading to clinical symptoms when the patient was exposed to oat.

Combined with the clinical history, these data suggest that the patient was sensitised to oat via the application of oat-based products to broken skin. As quoted in a previous article published within this blog, the head of AIRMed and senior author of this case study Professor O’Hehir states that: “This new study adds extra evidence to the argument for skin care preparations to be bland and to avoid agents capable of sensitisation, especially foods.”

Reference: Radhakrishna N, Prickett S, Phan T, Rolland JM, Puy R, O'Hehir RE. Anaphylaxis to oats after cutaneous sensitization by oatmeal in skin products used for the treatment of atopic dermatitis. J Allergy Clin Immunol Pract. 2016 Jan-Feb: 4;152-3

doi: 10.1016/j.jaip.2015.07.005

Development of intestinal gas capsules

By Dr Jodie Abramovitch

Many types of gases are produced within our digestive systems. Alterations in the type and amount of these gases can alter gut function, and potentially be a sign of disease.

Professor Peter Gibson - Head of the
Department of Gastroenterology

In a cross-disciplinary collaborative project including Monash researchers from the Department of Gastroenterology, a new intestinal gas capsule has been developed. These capsules has been designed to be swallowed so as to allow access to the gut in a non-invasive manner. Here they can sample the gases present and transmit their concentration and location (based on time lapsed following ingestion of the capsule) within the gut.

To test the capsules, pigs on high or low fibre diets were given the capsules. Pigs on a high fibre diet had higher concentrations of carbon dioxide (CO₂) and lower hydrogen gas (H₂) within their gastrointestinal tract than pigs given a low fibre diet. These findings were consistent with previous studies which measured gases in the guts of pigs on low and high fibre diets using classical (more invasive) techniques. As such, this study has shown that intestinal gas capsules can effectively provide information on the "where and what" regarding gas production in the gut, information that can only be determined presently by invasive techniques that are not possible to perform on humans.

Though the capsules require further refinement before they can be considered for use in humans, this study has shown that they have great potential to effectively and non-invasively detect gases within the gut. This will allow for a better understanding of the physiology of the gut  and permit easier detection and assessment of gut disorders within the clinic and inform treatment options.

Reference: Kalantar-Zadeh K, Yao CK, Berean KJ, Ha N, Ou JZ, Ward SA, Pillai N, Hill J, Cottrell JJ, Dunshea FR, McSweeney C, Muir JG, Gibson PR. Intestinal gas capsules: a proof-of-concept demonstration. Gastroenterology. 2016 Jan: 150;37-9
doi: 10.1053/j.gastro.2015.07.072

Perspectives on Women in Science

A recent publication in Baker IDI's Perspectives has focused on Women In Science. The article by A/Professor Rebecca Ritchie and Professor Bronwyn Kingwell was also published on Women’s Agenda last month.

A/Prof Rebecca Ritchie (left) and
Professor Bronwyn Kingwell (right)

"It is widely agreed that there is a great deal more work to be done to improve the representation of women at senior levels in Australian medical research. In this edition of Perspectives, we focus on gender inequality in the Australian science sector and explore how individuals and organisations are taking steps to effect change."

This publication is digital-only and is available via the Baker IDI website.

Ethanol exposure and traumatic brain injury

By Dr Jodie Abramovitch

Traumatic brain injury (TBI) is an important health issue, being a major cause of death and disability worldwide. When a TBI occurs in the absence of injury to the rest of the body, it is known as an isolated TBI (iTBI). Ethanol exposure or intoxication is commonly associated with iTBI. However, following injury, the effects of ethanol in the brain are unknown.

How does ethanol affect the brain?

Researchers from the Department of Epidemiology and Preventive Medicine (DEPM) and the Department of Surgery, alongside colleagues from the Alfred Hospital’s Emergency and Trauma Centre and National Trauma Research Institute, have recently investigated the association between ethanol exposure leading to iTBI and in-hospital mortality rates.

Slowing down age-related hearing loss

By Dr Jodie Abramovitch

Loss of hearing associated with age is a leading cause of disability amongst older people. Low level inflammation may damage blood vessels within the ear, leading to hearing loss. Furthermore, hearing loss may be associated with blood vessel damage within the eye, as well as loss of cognitive function. This suggests that there may be a common underlying inflammatory cause for each of these age-related conditions.

Can aspirin reduce age-related
hearing loss? 

Aspirin is a commonly used anti-inflammatory medication. It has a known role in helping treat blood vessel diseases and can inhibit the formation of blood clots.

Monash researchers from the School of Public Health and Preventive Medicine (SPHPM) are involved in a new study called ASPREE-HEARING. This study will assess the effect of aspirin on hearing levels in patients aged 70 years and older who are involved in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial.

Combatting superbugs – potential role of combination antibiotic therapy

By Dr Jodie Abramovitch

Infections caused by drug resistant (methicillin-resistant) Staphylococcus aureus (MRSA), a type of bacteria, can have serious health consequences. These infections are typically found in hospitals but can also occur within the community. MRSA is known as a superbug because it is able to survive many types of antibiotic treatments. 

Prof. Anton Peleg

Daptomycin is a ‘last-line’ antibiotic and is commonly used in the treatment of MRSA infections. However, there is evidence that daptomycin is unable to treat some MRSA infections which means alternative treatments are urgently required to prevent the spread of infection.

Monash researchers Dr Jhih-Hang Jiang and Professor Anton Peleg (Head of the Department of Infectious Diseases) study hospital-acquired infections and have recently focussed on how to combat daptomycin-resistant S. aureus. Samples of S. aureus from patients with infections were isolated and treated with different antibiotics, alone and in combination. When treated with both daptomycin and another antibiotic called gentamicin, antibiotic-resistant S. aureus was more effectively killed when compared to daptomycin treatment alone. However, it was noted that this approach may be associated with toxic side effects when used in patients.

This study concluded that combination therapy is an effective way to treat and limit the emergence of antibiotic-resistant strains of S. aureus, particularly in deep-seated, complicated infections. Further research is still required to balance the benefits of this approach with the potential risks. 

Reference: Jiang JH, Peleg AY. Daptomycin-Nonsusceptible Staphylococcus aureus: The Role of Combination Therapy with Daptomycin and Gentamicin. Genes (Basel). 2015 Nov; 6:1256-67