Diet determines drug dosage

THE UNIVERSITY OF SYDNEY

Cooking vegetables like cabbages, cauliflower and broccoli in curries can inhibit the enzyme CYP1A2.  Image: MaRussya/iStockphoto A University of Sydney PhD student has discovered the different diets and lifestyles of South Asians compared to Europeans could lead to the two groups requiring very different doses of medicines commonly used to treat illnesses such as depression and psychosis. Vidya Perera, a final year PhD student in the Faculty of Pharmacy, has found that people from South Asia could need lower doses of these medicines because they are likely to have lower levels of CYP1A2, an enzyme that metabolises drugs. "Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2, as was demonstrated in this study and previous studies in people of European background. The lower levels of CYP1A2 in South Asians, however, appears to be due to the common practice of cooking these vegetables in curries using ingredients such as cumin and tumeric, ingredients known to inhibit the enzyme, overriding the effect of the vegetables," Mr Perera explained. Mr Perera has just been declared the NSW winner of the AusBiotech/GlaxoSmithKline Student Excellence Awards as a result of his research. "I started out looking for genetic differences between the two groups to account for the differences in CYP1A2 activity. What was fascinating to discover is that genetic differences only accounted for 3 per cent of variability in CYP1A2 activity, while environment and lifestyle factors accounted for 35 percent of the differences," Mr Perera said. A total of 332 people took part in the study - 166 South Asians and 166 Europeans. CYP1A2 levels were measured by giving participants a caffeine tablet, and analysing CYP1A2 enzyme activity in saliva samples four hours later. Demographic, dietary and lifestyle information was obtained using a questionnaire. "Most drugs are approved in clinical trials conducted in Europe and North America using healthy, middle-aged European men," Mr Perera explained. "This is the first study to look at CYP1A2 activity in South Asians. Understanding the correct dose of a medicine is crucial to achieving beneficial results and avoiding adverse drug reactions." Professor Andrew McLachlan, Associate Dean (Research) in the Faculty of Pharmacy and Mr Perera's PhD supervisor, commented on the significance of this research. "The development and testing of medicines is a global enterprise. The highest population growth is occurring in South Asia, yet we know relatively little about how to translate research findings between different populations of people." "This research, for the first time, unpacks the complex interplay of factors that can affect how people breakdown and eliminate medicines from their body." "Past research has attributed differences between people from different geographical regions to result from genetic differences. This important research highlights how dietary and cultural factors can impact on pharmacological response." Mr Perera will travel to Adelaide this weekend to compete before a panel of judges in the national final of the AusBiotech/GlaxoSmithKline Student Excellence Awards. He will present his research on Sunday, with the winner to be announced on Monday. AusBiotech 2011 is the annual conference of AusBiotech and the premier biotechnology and life sciences conference for Australia and the Asia-Pacific, attracting over 1400 delegates from across the world each year. Editor's Note: Original news release can be found here.

How the ‘hospital superbug’ kills

MONASH UNIVERSITY

Transmission Electron Microscopy image of Clostridium difficile spores Image: Monash University An international team of scientists led by Monash University researchers has uncovered how a common hospital bacterium becomes a deadly superbug that kills increasing numbers of hospital patients worldwide.  The superbug accounts for an estimated $3.2 billion each year in health care costs in the United States alone. In research published today in PLoS Pathogens, team leader Dr Dena Lyras and lead author Dr Glen Carter, from the Monash University School of Biomedical Sciences, demonstrate how a naturally occurring mutation in the bacterium Clostridium difficile causes potentially life-threatening diarrhoea in hospital patients undergoing antibiotic therapy. Dr Lyras said C. difficile, which is able to colonise the colon when antibiotics, administered to treat other infections, have wiped out protective bacteria in the gut, causes a range of bowel disease symptoms, from mild diarrhoea to more chronic forms. "We've found that particularly dangerous strains of C. difficile are produced when a mutation effectively wipes out an inbuilt disease regulator, called anti-sigma factor TcdC. Not only are these strains hypervirulent, they are resistant to broad spectrum antibiotics, making them difficult to treat," said Dr Lyras. The results of the study suggest that all C.difficile strains carrying a similar mutation have the inherent potential to increase toxin production and become hypervirulent. Dr Lyras said this increased understanding underlying infection severity was timely as the incidence of hospital acquired infections was rising. "Over the past decade, there has been an astonishing increase in C.difficile infections throughout the world. Worryingly, the bacteria are also infecting people previously considered not at risk, including children and pregnant women. "This is a major public health issue. Hospitals, intended as places of healing, provide the perfect environment for the rapid evolution of pathogens that target susceptible patients.  "We must understand how these superbugs develop so we can develop treatments to combat them," added Dr Carter. “This study gives us a better understanding of these strains - how they develop, how they cause disease and why they are so harmful - so we can design new strategies to prevent, control and treat the rising rates of infection." Dr Lyras and Dr Carter collaborated with scientists from the Monash University Department of Microbiology and Monash Medical Centre, in Melbourne; the University of Glasgow, Kansas State University, and Institute Pasteur. The researchers were funded by the NHMRC, ARC, Wellcome Trust and NIH. Editor's Note: Original news release can be found here.

New muscles for nanorobots

UNIVERSITY OF WOLLONGONG

Image shows the tail region and insides of a futuristic microbot with the flagella-like tail, rotated by a length of the new carbon nanotube yarn torsional muscles. Image: University of Wollongong The possibility of a doctor using tiny robots in your body to diagnose and treat medical conditions is now one step closer to becoming reality thanks to research led by a team from the University of Wollongong. The development of artificial muscles small and strong enough to push the tiny Nanobots along has just been published in the journal, Science. Although Nanorobots (Nanobots) have received much attention for the potential medical use in the body, such as cancer fighting, drug delivery and parasite removal, one major hurdle in their development has been the issue of how to propel them along in the bloodstream. An international collaborative team led by researchers at UOW’s Intelligent Polymer Research Institute (IPRI), part of the ARC Centre of Excellence for Electromaterials Science (ACES), has developed a new twisting artificial muscle that could be used for propelling nanobots. The muscles use very tough and highly flexible yarns of carbon nanotubes (nanoscale cylinders of carbon), which are twist-spun into the required form. When voltage is applied, the yarns rotate up to 600 revolutions a minute, then rotate in reverse when the voltage is changed. Due to their complexity, conventional motors are very difficult to miniaturise, making them unsuitable for use in nanorobotics. “The twisting artificial muscles, on the other hand, are simple and inexpensive to construct either in very long, or in millimetre lengths,” according to ACES Chief Investigator, Professor Geoff Spinks. “This new, giant, rotating type of actuation will open up lots of new opportunities for micro-machines,” he said. Professor Spinks said the tiny artificial muscles can twist like those in the trunk of an elephant or the arm of an octopus. “In these appendages, helically wound muscle fibres rotate by contracting against an incompressible, bone-less core. The rotation in the helically wound carbon nanotubes used for the twisting artificial muscles is caused by an increase of liquid electrolyte volume within the yarn, Professor Spinks said. The research team working on this project includes Professor Spinks, Dr Javad Foroughi (Research Fellow with IPRI) and Professor Gordon Wallace (IPRI Director and the Executive Research Director of ACES). It also involves researchers from the University of Texas, Hanyang University and the University of British Columbia. Professor Wallace said the exciting breakthrough has been made possible through the tremendous efforts of a team of multidisciplinary researchers working from four different countries over a sustained period of time. “ACES continues to attract important collaborative research linkages with leading groups around the world and this is critical to maintain our position at the leading edge of scientific research,” Professor Wallace said. Editor's Note: Original news release can be found here.