Spring 2015 OVC Pet Trust Funded Projects

Comparison of three in-clinic tests to monitor the use of anti-platelet blood thinners in dogs

Various diseases can cause excessive blood clotting in dogs, resulting in thrombo-embolism (formation of clots and stroke orstroke-like events), which is often fatal. These diseases include hemolytic anemia, Cushing’s disease, hypothyroidism, intestinal and kidney diseases, and some neurologic (brain) conditions. Blood thinners may be used in an effort to decrease the risk of clot formation. The most commonly used drugs are clopidogrel and aspirin, which block platelets, the cells responsible for the first stage of clotting. These drugs are also used extensively in humans, where it is recognized that there is a large variation in individual response, and that they are ineffective in some diseases and in some people. In this study we will look at decreased platelet function in dogs treated with clopidogrel, aspirin, or a combination of both drugs.

Effect of decreased kidney function on tests for pancreatitis in cats

Pancreatitis is an important disease in cats, which varies in severity and can present as mild lethargy to fatal shock. For many years, no good tests were available to diagnose pancreatitis, other than abdominal surgery and biopsy of the pancreas. Both of which are unnecessarily invasive for the diagnosis of mild pancreatitis. Recently, two tests have emerged as useful for the diagnosis of pancreatitis in cats without surgery. We recently examined the effect of decreased kidney function on PLI in dogs by investigating the correlation between serum creatinine (a measure of kidney function) and PLI, and found that kidney function had only a weak effect on PLI in dogs. Our hypothesis is that the same is true for cats. We plan to measure PLI in cats with decreased kidney function that are considered to have a low likelihood of pancreatitis. During regularly scheduled appointments, a blood sample will be submitted for PLI. Cats with elevated PLI will have an ultrasound examination of the pancreas, and cats with abnormal ultrasounds will be excluded from the study. The correlation between serum creatinine and PLI will then be calculated.

Indication of canine T-Cell lymphoma in dogs

Lymphoma is a very common cancer in dogs that is frequently treated with chemotherapy. The cancer arises from a specific type of white blood cell called a lymphocyte. There are many different types of lymphocytes that can each give rise to different types of lymphoma. In dogs, “immunoblastic lymphoma” is the most common type (~60%). This type of lymphoma has a predictable response to chemotherapy, resulting in approximately 1 year of survival with good quality of life. The  other type of lymphoma is T-cell lymphoma (~40%), which is generally thought to have a poorer response to chemotherapy. T-cell lymphomas have different subtypes that have variable responses to chemotherapy. In this proposal, Dr. Bienzle and her team will address which specific T-cell lymphoma subtypes have unique response to chemotherapy, quality of life and survival; and whether T-cell lymphoma subtypes can be identified by traditional diagnostic methods.

Comparison of bronchoalveolar lavage suction techniques to sample feline lower airways

Cats are commonly taken to a veterinarian for respiratory diseases. A diagnostic test that may be recommended is a bronchoalveolar lavage (BAL), where a small volume of sterile fluid is put into the lung down the windpipe, and then suctioned back out. The fluid is then examined for the presence of cells and bacteria. Reasons for performing a BAL include coughing and changes on chest X-ray images. Side effects of BAL are generally minor. Despite the widespread use of BAL there is no standardized protocol. A recent email survey of specialty internists revealed that three quarters of internists use a specialized instrument (a bronchoscope) to perform BAL (B-BAL) in cats, whereas one quarter perform BAL without a bronchoscope (NB-BAL). We are investigating whether one of these techniques yields superior samples compared to the other.

Investigation of cellular regulatory mechanisms in central nervous system inflammatory disease in dogs 

Meningoencephalomyelitis is a condition of the central nervous system (CNS) that causes inflammation of the brain, spinal cord, and their membranes due to abnormally high numbers of eosinophils, a type of white blood cell, in the cerebrospinal fluid (CSF) with a high frequency of occurrence in dogs. Genetic and immune-mediated processes underlie the disease. Effective ways to provide prognoses and treatment options are very limited. New treatments are necessary to improve diagnosis and outcomes. MicroRNAs (miRNAs) are emerging as a useful model in numerous CNS conditions in humans (e.g.:  stroke and multiple sclerosis) and have shown impressive potential. This study represents a preliminary step towards the development of extensive miRNA profiles for individual diseases.

Targeted therapy to improve the chemotherapy response in dogs with bone cancer

Osteosarcoma (OSA) is the most common primary bone tumour in dogs. While the primary tumour can often be surgically removed, spread of the cancer to other organs results in limited survival beyond an average of 4 months. Chemotherapy treatment after surgery has improved survival to over a year on average, however eventually the cancer spreads in 90% of cases, and these dogs ultimately succumb to this disease. To improve treatment outcomes for OSA, our laboratory has investigated novel targets to improve the response to chemotherapy. Together with collaborators in Melbourne Australia, we conducted genetic knockdown studies and a high throughput screen of 131 potential drug candidates. Our recently published results strongly demonstrate that inhibition of a pathway known as PI3K/mTOR may be a promising therapeutic target in OSA. Our research seeks to improve the successful translation of promising drugs by prioritizing those agents that demonstrate the most promise in the laboratory when tested against all three species (mouse, human, dog). We feel that these agents will have the greatest chance of success in future clinical trials in both dogs and people.

Dose Reduction and Cardiovascular Effects of Anesthetic Induction with Propofol or Alfaxalone with or without Midazolam in Clinical Canine Patients

Dogs commonly require general anesthesia for diagnostic and/or surgical procedures in primary care practices and referral institutions. Induction of anesthesia should be rapid, without inflicting significant stress to the animal’s heart and lungs and tominimize the impact of anesthesia on the primary disease or cause the development of new problems. A common protocol for providing anesthesia to a patient, involves the use of sedation with the opioid fentanyl to facilitate handling and provide pain control of the patient and then induction with propofol or alfaxalone. Both of these however, depress cardio-respiratory function. Often, a benzodiazepine is administered as a co-induction anesthetic immediately after the administration of propofol or alfaxalone to potentially decrease the dose and promote better cardio-respiratory stability which is beneficial in compromised dogs requiring emergency surgery.

Impact of biofilm formation on the efficacy of commonly used antibiotic

Surgical site infections (SSIs) are an inherent risk of any surgical procedure and are an increasing cause of patient morbidity, prolonged hospitalization, increased treatment costs and owner/veterinarian frustration. The objective of our study is to evaluate the impact of biofilm formation on the MIC (minimum inhibitory concentration) of S. pseudintermedius for several commonly used antimicrobials in small animal practice. S. pseudintermedius has rapidly emerged to become the leading cause of SSI soft tissue infections in dogs. SSIs can result in considerable morbidity for our patients and result in much greater treatment costs for pet owners. Biofilm formation has been hypothesized as a virulence factor in SSIs in humans, however, there has been very little study in this area in veterinary medicine. Further understanding of the role of biofilm formation in S. pseudintermedius SSIs is required in an attempt to develop treatment strategies for this clinically significant canine pathogen.

Canine plasma solublthrombomodulin as aindicator of inflammatordisease severity

Response to injury or infection involves complex interactions between components of the immune, inflammation, and coagulation systems, in order to protect and restore normal organ function. Coagulation is the process of blood clot formation and the molecule, thrombin, plays a diverse role in the inflammatory response. Thrombin has multiple functions including activation of other molecules to mediate specific cellular events. One such molecule is thrombomodulin (TM), a protein normally present on the surface of cells that line blood vessels, known as endothelium. Thrombomodulin is essential for regulating thrombin generation and when the process is dysregulated, or excessive, it may cause adverse inflammation or coagulation. Many diseases are associated with a severe inflammatory response, which results in reduced TM expression, limiting TM’s regulatory ability. This reduction is in part due to its release as a soluble form (sTM) into the bloodstream.  Lower cell surface TM expression and higher sTM expression may correlate with severity of inflammation in diseased or damaged tissues, which may provide prognostic information for dogs with severe inflammation.

Measurement of pre-treatmenlevels and early changes in serum cytokines of dogs with multicentric lymphoma treatewith a CHOP protocol

Lymphoma is one of the most common cancers in dogs and cats, with an annual incidence being estimated to range between 13 and 24 per 100,000 dogs at risk. It comprises 7% to 24% of all canine cancers, and the frequency is continuing to increase. The gold standard for treatment in dogs, as well as in humans, integrates a multi- agent chemotherapy protocol called CHOP, which combines three different chemotherapies with the steroid Prednisone. However, the response to therapy can vary widely between patients, from cure to no response and rapidly fatal disease.  The goal of this research project is to evaluate the relationship between circulating cytokines and lymphoma before and after chemotherapy treatment. We expect to learn new insights on how lymphoma develops and get a better prediction of prognosis for dogs with lymphoma.

Protocol development fomicrowave ablation of bone idogs - a novel cancer therap

Microwave ablation therapy is performed in human medicine to treat various cancers and has shown to reduce overall costs, morbidity, and mortality compared to standard surgical procedures. It has been proven successful in the palliative treatment of bone cancer, primarily to alleviate pain. During the procedure an antenna is inserted through the skin with imaging guidance, endoscopically or intra-operatively, and into the cancer that is subsequently heated and destroyed. Microwave ablation holds great promise for veterinary patients as a minimally invasive cancer therapy. This minimally invasive therapy would be an additional asset in limb sparing techniques, and a tremendous help to decrease pain in patients with painful bone metastases. This project will focus on developing a procedure to treat bone cancer in dogs with microwave thermal ablation therapy, and determine its feasibility prior to use in clinical trials. The ultimate goal of our work with microwave ablation therapy is to provide a minimally invasive, efficacious and cost-effective therapeutic option for the treatment of  various cancers in dogs.