Tag Archives: University of Illinois

Hunting dogs may benefit from antioxidant boost in diet

Free radicals, those DNA-damaging single-oxygen atoms, are produced in spades during exercise. Dogs that exercise a lot, like hunting dogs, may need to consume more antioxidants than their less-active counterparts to protect against this damage. But what diet formulation best meets the needs of these furry athletes? A new University of Illinois study provides some answers in a real-world scenario.

Hunting dogs

Researchers visited a kennel of American Foxhounds in Alabama over the course of a hunting season, providing one group a high-performance commercial diet and another group a test diet similar to the commercial diet, but with added antioxidants (vitamins C and E, and lutein), zinc, and taurine. During the study, dogs from both groups went on two to three hunts per week, each 2 to 5 hours in length.

“We think of it as unstructured endurance exercise. They’re not running the entire time. They might stop to sniff or go more slowly to pick up a scent,” says Kelly Swanson, corresponding author on the study and Kraft Heinz Company Endowed Professor in Human Nutrition in the Department of Animal Sciences and the Division of Nutritional Sciences at U of I.

Before starting the diets and on four occasions during the seven-month study, researchers took blood samples from the dogs to examine oxidative stress markers and other blood metabolites.

“We hypothesized that dogs fed the test diet would have a lower concentration of oxidative stress markers and improved performance compared to the dogs fed the commercial diet,” Swanson says. “It turns out performance wasn’t affected by diet, but the test diet did improve indirect measures of oxidative stress. Therefore, improved performance may be expected with more strenuous exercise when metabolic demands are higher.”

The amino acid taurine, once thought to be non-essential for dogs but now recognized as an important nutrient for heart health, declined over the course of the season for dogs fed the commercial diet. The same pattern occurred with vitamin E. Although one dog did come close to a critically low level of taurine during the study, all dogs fed the commercial diet stayed within the normal range for all blood metabolites.

For dogs fed the test diet, taurine and vitamin E levels were maintained at or above the baseline. The results suggest to Swanson and his co-authors that these compounds are compromised in athletic dogs over months of unstructured exercise, and more-active dogs such as sled dogs may experience greater depletion.

“We can conclude that athletic dogs may benefit from supplementation of vitamin E and taurine to minimize oxidation and maintain taurine status,” he says.

The article, “Longitudinal changes in blood metabolites, amino acid profile, and oxidative stress markers in American Foxhounds fed a nutrient-fortified diet,” is published in the Journal of Animal Science [DOI: 10.1093/jas/skx070]. Funding was provided by The Nutro Company.

Source:  University of Illinois press release

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Scientists test nanoparticle drug delivery in dogs with osteosarcoma

At the University of Illinois, an engineer teamed up with a veterinarian to test a bone cancer drug delivery system in animals bigger than the standard animal model, the mouse. They chose dogs – mammals closer in size and biology to humans – with naturally occurring bone cancers, which also are a lot like human bone tumors.

wikimedia-commons-photo-of-bmd

Dogs with naturally occurring cancers are more similar in size and biology to humans than are other mammals, such as mice. Public domain photo: Wikimedia Commons

In clinical trials, the dogs tolerated the highest planned doses of cancer-drug-laden nanoparticles with no signs of toxicity. As in mice, the particles homed in on tumor sites, thanks to a coating of the drug pamidronate, which preferentially binds to degraded sites in bone. The nanoparticles also showed anti-cancer activity in mice and dogs.

The researchers report their results in the Proceedings of the National Academy of Sciences.

These findings are a proof-of-concept that nanoparticles can be used to target bone cancers in large mammals, the researchers said. The approach may one day be used to treat metastatic skeletal cancers, they said.

The dogs were companion animals with bone cancer that were submitted for the research trials by their owners, said U. of I.  Professor Dr Timothy Fan, who led the study with materials science and engineering Professor Jianjun Cheng.  All of the dogs were 40 to 60 kilograms (88 to 132 pounds) in weight, he said.

“We wanted to see if we could evaluate these drug-delivery strategies, not only in a mouse model, but also at a scale that would mimic what a person would get,” Fan said. “The amount of nanoparticle that we ended up giving to these dogs was a thousand-fold greater in quantity than what we would typically give a mouse.”

Using nanoparticles with payloads of drugs to target specific tissues in the body is nothing new, Cheng said. Countless studies test such approaches in mice, and dozens of “nanopharmaceuticals” are approved for use in humans. But the drug-development pipeline is long, and the leap from mouse models to humans is problematic, he said.

“Human bone tumors are much bigger than those of mice,” Cheng said. “Nanoparticles must penetrate more deeply into larger tumors to be effective. That is why we must find animal models that are closer in scale to those of humans.”

Mice used in cancer research have other limitations. Researchers usually inject human or other tumor cells into their bodies to mimic human cancers, Fan said. They also are bred to have compromised immune systems, to prevent them from rejecting the tumors.

“That is one of the very clear drawbacks of using a mouse model,” Fan said. “it doesn’t recapitulate the normal immune system that we deal with every day in the person or in a dog.”

There also are limitations to working with dogs, he said. Dogs diagnosed with bone cancer often arrive at the clinic at a very advanced stage of the disease, whereas in humans, bone cancer is usually detected early because people complain about the pain and have it investigated.

“On the flip side of that, I would say that if you are able to demonstrate anti-cancer activity in a dog with very advanced disease, then it would be likely that you would have equivalent or better activity in people with a less advanced stage of the disease,” Fan said.

Many more years of work remain before this or a similar drug-delivery system can be tested in humans with inoperable bone cancer, the researchers said.

Source:  Illinois News Bureau media release

Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

Drug trials in pet dogs with cancer

Physiological similarities between dogs and humans, and conserved genetics between some dog and human cancers, can allow pet dogs to serve as useful models for studying new cancer drugs, says Dr Timothy Fan of the University of Illinois.

Timothy Fan, professor of veterinary clinical medicine. With his personal dog, Ember

Timothy Fan, professor of veterinary clinical medicine. With his personal dog, Ember  photo by L. Brian Stauffer

In a meeting sponsored by the National Cancer Policy Forum of the National Academies’ Institute of Medicine in Washington, D.C., Fan and 15 other experts in the field described the benefits of using pet dogs with naturally occurring (rather than laboratory-induced) tumors in early cancer drug trials.

“We have a lot of dogs in the United States, approximately 70 million of them, and it’s believed that about 25 percent of pet dogs will develop some form of cancer in their lifetime,” he said. “We’re using dogs to help guide drug development for people, but at the same time we’re offering new, innovative therapies that would otherwise never be available to dogs, to help them as well.”

Several attributes make pet dogs attractive subjects for such studies, Fan said.

“Dogs tend to develop cancer as a geriatric population, just like people,” he said. “Because the tumors develop spontaneously, there is heterogeneity in that tumor population, as a human being would have. The size of the tumors and the speed of growth of those tumors are comparable in dogs and human beings. So there are many attributes of a dog that develops cancer spontaneously that recapitulate the biology that we see in people.”

Some studies have already begun using dogs to test new cancer therapies. Starting in 2007, for example, Fan began testing an anti-cancer drug called PAC-1  in pet dogs with naturally occurring lymphomas and osteosarcomas. The results in dogs allowed the scientists to advance PAC-1 as a potential therapy against human cancers. The drug is now in phase I human clinic trials.

“Another example in which dogs have been important in demonstrating drug activity was an anti-cancer compound produced by the pharmaceutical company Gilead Sciences,” he said. “The company produced a pro-drug, which must be activated by a naturally occurring enzyme in human leukocytes before it can become effective. Mice and rats lack this enzyme, but dogs have it, so the compound was tested in dogs.”

There also are limitations to the use of pet dogs in cancer drug trials.

“There are some tumors that will not be that relevant,” Fan said. “Colon cancer, for example, is heavily driven by diet, and we don’t see much colon cancer in dogs. So pet dogs might not be a suitable model for colon cancer in humans.”

“There is heterogeneity in the human population and in dogs. So I would argue that if your drug agent produces positive results in dogs, that would give me greater confidence that those findings would be translatable to people.”

Source:  University of Illinois media release

The migration of dogs in the Americas

A new study suggests that dogs may have first successfully migrated to the Americas only about 10,000 years ago, thousands of years after the first human migrants crossed a land bridge from Siberia to North America.

Photo by Angus McNab

Photo by Angus McNab

The study, which looked at the genetic characteristics of 84 individual dogs from more than a dozen sites in North and South America, is the largest analysis so far of ancient dogs in the Americas. The findings appear in the Journal of Human Evolution.

Unlike their wild wolf predecessors, ancient dogs learned to tolerate human company and generally benefitted from the association: they gained access to new food sources, enjoyed the safety of human encampments and, eventually, traveled the world with their two-legged masters. Dogs also were pressed into service as beasts of burden, and sometimes were served as food, particularly on special occasions.

Their 11,000- to 16,000-year association with humans makes dogs a promising subject for the study of ancient human behavior, including migratory behavior, said University of Illinois graduate student Kelsey Witt, who led the new analysis.

“Dogs are one of the earliest organisms to have migrated with humans to every continent, and I think that says a lot about the relationship dogs have had with humans,” Witt said. “They can be a powerful tool when you’re looking at how human populations have moved around over time.”

Human remains are not always available for study “because living populations who are very connected to their ancestors in some cases may be opposed to the destructive nature of genetic analysis,” Witt said. Analysis of ancient dog remains is often permitted when analysis of human remains is not, she said.

Previous studies of ancient dogs in the Americas focused on the dogs’ mitochondrial DNA, which is easier to obtain from ancient remains than nuclear DNA and, unlike nuclear DNA, is inherited only from the mother. This means mitochondrial DNA offers researchers “an unbroken line of inheritance back to the past,” Witt said.

The new study also focused on mitochondrial DNA, but included a much larger sample of dogs than had been analyzed before.

Source:  University of Illinois press release

 

Pet obesity at the molecular level

A University of Illinois research team led by Professor Kelly Swanson has published research which describes how nutrients and biological compounds in foods can affect gene expression in animals.

The research will help to understand the underlying reasons for obesity in pets.  Professor Swanson explains that obesity has its roots in the domestication of dogs.  Because dogs no longer hunt or compete for their food and are speyed or neutered (so not having to mate),  the typical dog has much smaller energy requirements than its forefathers.

The research team explains that when more energy (food) is consumed than is required, it is stored as fat in the adipose tissue (fat tissue).  Adipose tissue secretes more than 50 substances known as adipokines, which are cell-signaling molecules that are involved in metabolism, immunity and inflammation.

In obese dogs, levels of the adipokine leptin increases while the levels of the  adipokine adiponectin decreases.

The researchers aim to study obesity at the molecular level, so they can help to prevent it happening.

Source:  University of Illinois media statement