Canadians spend about $27 billion each year on pharmaceuticals, which represents the largest component of private health care costs. For some, this means significant financial hardship. For others, the costs are too high, prohibiting access to necessary care. To date, very little attention has been paid to equity in access to prescription drugs, even though a central goal of Canadian health care policy is to promote access to necessary health care. British Columbia’s Pharmacare program of income-based drug coverage has been proposed as a national standard. Gillian Hanley is examining the degree of income-related inequity in accessing prescription drugs, before and after the program was introduced in 2003, to assess the potential impact of national implementation. She is looking at how a change in coverage affects equity of access to medicines at a population level as well as within and across population subgroups. Previous research by Hanley and her colleagues has shown that the major impact of BC’s Pharmacare program is one of redistributing costs from public to private sources and across various income levels. Part of this research suggested that individuals of higher income generally have higher total drug expenditures. As previous research has shown that higher income individuals are often healthier than those of lower income, their higher drug spending is unexpected and warrants further examination. . Her goals are to offer policy makers insight into how to improve current Pharmacare models and to provide researchers with new methods to examine equity in access to medicines and health services.
Research Location: University of British Columbia - Point Grey
Leptin Regulation of Hepatic Glucose and Lipid Metabolism
More than 60,000 Canadians are diagnosed with type 2 diabetes each year, making it one of the fastest growing diseases in Canada. About 80 per cent of people with type 2 diabetes are also obese, a deadly combination that results in many long-term complications and makes diabetes the seventh leading cause of death in Canada. It is essential, therefore, to improve our understanding of the links between diabetes and obesity. The fat cell-derived hormone leptin may be a key factor linking the two. Leptin is well known to influence body weight through its ability to depress appetite and increase energy expenditure. However, leptin also has profound direct effects on metabolism. For example, mice completely deficient in leptin or the leptin receptor are obese and also develop increased fat in the blood, increased build-up of fat in tissues, and type 2 diabetes. While it is clear that leptin can act on the brain to regulate body weight, it is less clear how leptin influences glucose and fat metabolism. This is the focus of Frank Huynh’s research; in particular, the role leptin signalling in the liver may have on glucose and fat metabolism and if dysregulation of these pathways can contribute to type 2 diabetes. A better understanding of the mechanisms of leptin action would help clarify its role in the development of diabetes and obesity, potentially pointing the way to better treatment strategies.
Autonomic dysreflexia and axonal plasticity in sympathetic ganglia following spinal cord injury
Each year, 35 people per million in Canada sustain a spinal cord injury. Apart from the well known motor and sensory dysfunctions, there are a number of autonomic nervous system changes that can occur after spinal cord injury, including bladder, bowel, thermoregulatory, sexual and cardiovascular dysfunctions. These changes significantly affect the overall quality of life of individuals with spinal cord injury. One cardiovascular dysfunction that commonly develops following high spinal cord injury is called autonomic dysreflexia. Autonomic dysreflexia is a life-threatening condition that is characterized by sudden increases in blood pressure triggered by normal touch below the level of injury. These episodes can be extremely uncomfortable for patients as they are often accompanied by pounding headaches, upper body flushing and feelings of anxiety. Furthermore, as these episodes are often triggered by routine daily events, such as catheterization, they can significantly interfere with rehabilitation programs and work schedules. The cause of autonomic dysreflexia is unknown. In her research, Jessica is looking at how spinal cord injury changes sympathetic nerve cells – cells that are involved in regulating blood pressure by speeding up the heart and contracting blood vessels. One possibility is that there are unusual new connections formed between sensory and sympathetic nerve cells after spinal cord injury; so that a normal touch, which did not cause increased blood pressure before injury, is abnormally connected to sympathetic nerve cells after injury, causing increased blood pressure. Ultimately, Jessica hopes her research will help lead to the development of therapeutic strategies to prevent autonomic dysreflexia’s devastating effects on people with spinal cord injury.
Using real-time fMRI to modulate metacognitive thought processes in patients with recurrent unipolar depression
About 15 per cent of adults experience major depression at some time in their lives. This debilitating mental disorder can cause depressed moods, loss of energy, insomnia and, in severe cases, suicidal ideas and acts. Although current treatments such as antidepressant drugs and psychotherapy help a majority of patients, a significant number of people have a high rate of relapse. In recent years, several cognitive therapies have been developed to try to prevent relapse. One successful method trains patients to increase their ability to reflect on and change the direction of their own thoughts (called meta-cognitive awareness). Depression involves a reduction in certain parts of the brain. Functional Magnetic Resonance Imaging (fMRI) scans show depressed people have abnormally low activity in the front part of the prefrontal cortex, a region of the brain involved in planning cognitive behaviours and pleasure. fMRI scans also show an increased activation in this area of the brain when patients use reflective thinking. Kamyar Keramatian is investigating whether normal subjects and patients with depression can be trained to improve their own brain activation, by combining self-reflective therapy with real-time fMRI; a new tool that allows patients and researchers to see brain activation data as it is collected. If so, this approach could be an effective way to treat people who do not respond to conventional therapies.
The role of the Rap1 GTPase in mediating the inflammatory and anti-microbial functions of macrophages
Large, white blood cells (called macrophages) play a crucial role in protecting the body against harmful viruses, bacteria and other substances, such as pollen, that the immune system recognizes as foreign. These cells trap the foreign substance and signal other cells in the immune system to start the inflammatory process needed to destroy them. Normally, the body tightly regulates the process ensuring that once the invader is destroyed, the inflammatory process is shut down to minimize damage to and promote healing in surrounding tissue. However, sometimes the process goes awry, such that the inflammatory process persists, which can lead to a variety of autoimmune diseases, including hay fever, atherosclerosis, and rheumatoid arthritis. Victor Lei is exploring whether a protein called Rap 1 is involved in activating the immune response to microbial infections by helping white blood cells find infected tissue and initiate inflammation. He is looking in particular to discover whether appropriate Rap1 levels create an effective response to infection, while excessive levels contribute to chronic inflammatory response that could lead to autoimmune diseases. The results of this research could help in the development of drugs that control Rap 1 activity to more effectively combat infections and prevent or minimize the chronic inflammation responsible for arthritis and other conditions.
Study of intercellular barrier alterations in enterocytes during Campylobacter jejuni pathogenesis
Campylobacter jejuni (Cj) is the leading cause of bacterial food poisoning in the world. Each year about 300,000 Canadians are infected by these highly invasive bacteria through ingestion of undercooked meats or dairy products. An acute infection causes diarrhea, fever, vomiting, and, occasionally, death. Cj infection may also lead to Guillain-Barré Syndrome, an autoimmune disease that causes weakness or tingling in the legs and arms. In some cases, symptoms can become so severe that the patient is almost totally paralyzed. Most people recover, although some continue to have some degree of weakness. Ann Lin is researching how Cj bacteria cause disease in the gastrointestinal tract. Cj is predominantly found in the first and last sections of the small intestine and the colon. The bacteria penetrate layers of cells in the intestine and infect underlying tissues. Lin is examining whether this process disrupts the intercellular junctions that provide integrity for host epithelial cells. Disrupting this barrier is believed to contribute to diarrhea, but the molecular process is not well understood. Lin will determine whether Cj causes gastrointestinal disease by damaging the barrier. Ultimately, her findings could lead to the development of new methods of preventing Cj infection.
Correlation Between Results from a New Magnetic Resonance Imaging Technique to Measure Myelin in the Spinal Cord and Somatosensory Evoked Potentials
Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool due to its ability to provide soft tissue contrast with high spatial resolution. Clinicians and researchers alike value MR images both for diagnosis and characterization of changes cause by disease. Recent advances have been made using MRI to image central nervous system white matter and investigate diseases that affect the white matter (such as Multiple Sclerosis), and damage to the spinal cord. The term “white matter” is derived from the white colour of nerve tracts. It appears white because of the layers of fat wrapped around each nerve fibre, called the “myelin sheath”. If the myelin sheath has been degraded or broken down, transmission of information along the fibre can be slowed down or lost completely. In the case of a narrowing of the spinal canal, the invertebral discs slip out of place and put pressure on the spinal cord, damaging the white matter tracts, resulting in symptoms like a feeling of numbness or tingling in the hands or feet. Somatosensory evoked potentials (SSEP) are a current clinical tool used to detect myelin degradation and nerve damage in the spinal cord. However, SSEP measurements are limited to only sensory pathway nerves, and cannot locate damage throughout the entire spinal cord. The UBC MRI Research Group has recently developed an MRI technique to measure myelin content in vivo, termed “myelin water imaging” (MWI), which can be applied throughout the brain and spinal cord. Erin MacMillan is applying the MWI technique to healthy adults and people suffering from narrowing of the cervical spinal canal. She hopes to find that MWI provides results consistent with SSEP measurements in sensory pathways, and identifies myelin degradation throughout the cervical spine. In addition, she will compare patient results from before and after surgery in the hopes of finding that the white matter has been repaired. If MWI proves to be an accurate measurement of myelin in the spinal cord, it could potentially be used to track myelin content during new spinal cord injury treatments aimed at degrading myelin in an effort to encourage nerve fibre repair.
Characterization of a kinase implicated in kinetochore function during S phase
Chromosomes, which are a compacted form of DNA, must be accurately duplicated and separated into two new daughter cells during each cell cycle. Genetic instability arises when chromosomes are separated improperly. This error is the source of many diseases, such as cancer and Down’s syndrome. Accurate chromosome separation relies on machinery assembled on each chromosome called the kinetochore. The regulation of the kinteochore is essential for cellular fitness and prevention of genetic instability. Understanding the mechanism by which the kinetochore is regulated will lead to a better view of cellular division and will provide insight into the treatment of diseases such as cancer. Because chromosome separation is a fundamental cellular process in all types of cells, Jennifer McQueen is using budding yeast as a model to study chromosome segregation. She is using many genetic and biochemical tools to examine the involvement of the Mck1 kinase in chromosome separation. Her project aims to discover a new role for the Mck1 kinase in kinetochore function and to produce a new model of kinteochore regulation that is applicable to human health.
Impact of community engaged arts on the health status of older adults
With the number of seniors in Canada’s population increasing, more older adults are potentially dealing with chronic or recurring health issues. Given this trend, there’s an essential need to identify health resources available to these individuals and to evaluate the effectiveness of these resources in impacting health status. Recent research has show that that creative involvement in the arts positively impacts the health of older adults. Elaine Moody is investigating how a community-based art project impacts health among its older adult participants. She is studying groups of seniors in the Vancouver area who are currently participating in community-engaged arts projects focused on developing creative and artistic abilities, and providing opportunities to meaningfully contribute to their communities. Through a questionnaire and a series of interviews, Elaine is collecting information about the health status of the participants, including physical, mental and social health, and overall well-being. Using statistical methods, she is examining the information obtained to determine if health status has improved over the course of the study. Her overall aim is to provide a clearer understanding of the health benefits of participating in community engaged arts for older adults.
Modulation of Cav3.2 T-type calcium channels through neuronal nitric oxide synthase activity
Normal brain activity involves the controlled transmission of electrical impulses across networks of neurons (nerve cells). Occasionally, undesired electrical activity occurs within cellular networks and a response is necessary to suppress this outburst. Kirk Mulatz is investigating a negative feedback mechanism that allows neurons to inhibit this atypical electrical activity. He is focusing on the role of T-type calcium ion channels in generating this aberrant electrical activity, and exploring the effectiveness of inhibiting characteristics of the channels to inhibit the activity. Investigations into negative feedback mechanisms both increase understanding of normal brain activity and how cells respond to abnormal activity. A number of neuronal disorders such as epilepsies, mood disorders and chronic pain are associated with atypical brain activity, and the feedback mechanism that Mulatz is researching may contribute to restoring normal activity across cellular networks.