CAHF Research Grants: 2014-15

Metformin: a new potential cancer drug for dogs?

Drs. M. Casey Gaunt, Charlotte Johnson, Valerie MacDonald Dickinson and Trisha Dowling, WCVM; and Ryan Dickinson, Prairie Diagnostic Services

Metformin is a drug that has been used to manage type-2 diabetes mellitus in humans. Recent studies have shown that the drug may also have the ability to decrease the incidence of — or suppress — certain types of cancer that affect people. Dogs are susceptible to many types of cancers, and similar to human medicine, treatment options for cancer are limited and can have undesirable side effects.

Since metformin is proven to be effective and safe in humans, veterinary researchers such as Dr. Casey Gaunt and his colleagues are investigating its use as a potential cancer treatment in animals.

As a first step, the researchers are striving to characterize the pharmacokinetics of metformin in healthy dogs by taking blood samples at regular intervals for seven days after starting oral doses of metformin twice daily. This data will provide information on how the drug moves through the body, how it is metabolized, and how long it remains in the body.

The study’s second objective is to determine an effective and safe dose of metformin in dogs. The researchers will deliver increased doses of metformin and take regular blood samples for seven days – ultimately trying to deliver a dose that results in blood levels similar to human and feline treatments.

As a final goal, Gaunt and the research team will also investigate the drug’s physiological mechanism(s) to determine how it works — something that remains unknown, even in humans. The study’s results will provide human and veterinary researchers with useful information as they work together in the ongoing battle against cancer.

Investigating the connection between E.coli infections and cancer

Drs. Valerie MacDonald, Charlotte Johnson, and Joseph Rubin, WCVM

Escherichia coli (E. coli) is the most common cause of urinary tract infections in dogs, and those animals with cancer are at greater risk of infection. While veterinarians have effectively treated this common bacterium with antibiotics for many years, the emergence of antimicrobial resistance is presenting a significant treatment challenge for clinicians.

MacDonald and her research associates aim to better understand the epidemiology of E. coli in canine cancer patients: how common is antibiotic resistance in E. coli from dogs diagnosed with cancer and are canine cancer patients that develop urinary tract infections (UTIs) infected by their resident strain of the bacterium?

To answer the first question, team members will screen canine cancer patients for antibiotic-resistant E. coli. Secondly, the researchers will look at dogs with bladder cancer and compare E. coli causing UTIs in these dogs with E. coli isolated from rectal swabs to determine whether UTIs are caused by a dog’s own E. coli.

This research will help clinicians understand, treat and prevent E. coli infections in animals — especially in those that have cancer and are more susceptible to developing infections.

Examining the details of a common bacterium found in dogs

Drs. Joseph Rubin and Matthew Gaunt, and Madalagama Appuhamilage Roshan Priyantha, WCVM

While Staphylococcus pseudintermedius (SP) is a common bacterium that can be found in up to 90 per cent of healthy dogs, it’s also associated with skin, ear, urinary tract and hospital-acquired infections in dogs.

Historically, infections caused by SP could be easily treated with common antibiotics. Since the late 2000s, antibiotic resistance (including methicillin resistance) has been increasingly encountered in Western Canada. Methicillin-resistant S. pseudintermedius (MRSP) is problematic because these bacteria are resistant to many of the most important and commonly used antibiotics. This presents a major challenge for veterinarians to treat their patients.

Dr. Joseph Rubin and his research team are conducting an antibiotic resistance surveillance study to determine if the prevalence of drug-resistant SP is increasing in Saskatoon dogs. This study aims to help local veterinarians understand the frequency of drug-resistant SP and to help them more effectively identify and treat their patients with the appropriate antibiotics.

The researchers also propose a detailed investigation of SP to understand what properties of the bacterium make it more likely to cause skin versus bladder infections. An understanding of these bacterial mechanisms of disease will help clinicians diagnose and treat SP-infected patients.

Evaluating chest tube fluids may provide better animal care

Drs. Sherisse Sakals, Germaine Hung, Casey Gaunt, Joseph Rubin and Greg Starrak, WCVM

Veterinarians will often insert a chest (thoracostomy) tube in an animal’s chest cavity if air or fluid accumulates in the pleural space (the tiny area between the two layers of the pleura, the thin covering that protects and cushions the lung). The chest tube aids in managing the condition, but it can cause negative side effects. For example, the presence of the tube itself can stimulate fluid production and use of chest tubes may result in infections.

Current clinical guidelines recommend that veterinarians remove chest tubes once fluid production is reduced to one to two millilitres per kilogram per day. However, Dr. Sherisse Sakals and her research collaborators point out that there is little scientific evidence to support this suggestion.

In their study, the WCVM researchers will work to quantify and characterize the fluid that’s created when using a chest tube. They also aim to evaluate the risk of infections associated with this procedure. Knowing the nature and amount of fluid produced as a result of the tube itself will be a useful clinical tool. Better understanding of the difference between fluid produced due to the tube and that produced because of a disease may aid in clinical decision making about therapeutic options in a sick animal.

Data from this research will provide veterinarians with better guidelines for therapies requiring chest tubes and will assist them in monitoring diseases. Ultimately, using chest tubes more effectively and reducing the amount of time they’re used in treatments may reduce hospital stays, decrease owner costs and result in an overall improvement in animal care and welfare.

A new method for detecting kidney disease in cats

Drs. Elisabeth Snead, James Montgomery, and Jewel Milo, WCVM; Drs. Carl Wesolowski and Michal Wesolowski, U of S College of Medicine

Kidney disease is one of the most common disorders and causes of death in dogs and cats. However, early detection, diagnosis and treatment may be key in preventing further damage and increasing animal survival and quality of life.

Kidney function can be assessed in a variety of ways, but in clinical practice, blood work is commonly evaluated to identify levels of metabolites (e.g. creatinine and urea).  This is problematic since elevations in these values do not occur until late in the disease – only after 75 per cent of the kidney function is lost. In addition, these parameters can be affected by many factors that are not related to kidney disease (for example, diet).

Assessment of kidney function by measurement of the glomerular filtration rate (GFR) is considered the gold standard for determining kidney function. Measurement of GFR provides significant advantages over measurement of kidney values in the blood, both for the early detection of kidney disease and for providing a more accurate way to monitor kidney function over time. However, GFR determination still remains underused as a diagnostic, monitoring and prognostic test in veterinary medicine.

In human medicine a new method of GFR determination called the Tikhonov gamma variate (Tk-GV) method has been proposed. Based on retrospective data, the Tk-GV method allows for more accurate and precise determination of kidney function. To date, this method of analysis for GFR determination has not been applied in veterinary patients. Dr. Snead and her research group aim to compare the accuracy of the Tk-GV method to three more commonly used methods of GFR measurement in healthy cats.

If this new approach proves to be more reliable than existing methods, the research team hopes that more veterinarians will adopt it into routine practice.

SAMe may have antioxidant potential in companion animals

Drs. Katharine Woods and Astrid Kjaergaard, WCVM

Oxidants are compounds that cause damage to living cells and tissues within the body by a process that is known as oxidative stress. Conversely, antioxidants are compounds that neutralize oxidants and help prevent tissue damage. There’s a delicate balance of both oxidants and antioxidants in all animals’ bodies, and if this balance is disrupted, diseases can arise.

A number of diseases – including cancer, heart disease, trauma and lung disease – have been associated with high levels of oxidants that lead to tissue damage and organ failure.

In this preliminary study, Drs. Katharine Woods and Astrid Kjaergaard will focus on a particular antioxidant – S-adenosylmethionine (SAMe) – which they believe could be used as a therapy for diseases that are caused by excessive oxidants.

In their research, they will administer oral doses of SAMe to healthy dogs and examine known markers of oxidative stress in their blood and urine samples. If the dogs’ samples show signs of decreased oxidative stress after 30 days of oral SAMe supplementation, this study could be the first step in determining whether this inexpensive method could eventually be used to safely treat a variety of common illnesses that occur in companion