Research News from the College of Veterinary Medicine
Excerpted from stories by Jim Barlow, UI News Bureau

Osteoporosis drugs found to combat malaria, other diseases
A series of bisphosphonate drugs already approved to treat osteoporosis and other bone disorders in humans carry potent anti-parasitic activity, offering a new approach to the treatment of malaria, sleeping sickness, and AIDS-related infections such as toxoplasmosis.

Parasitic protozoan diseases are the world’s most widely spread human health problem. An estimated 3 billion people suffer from one or more parasitic infections. Plasmodium falciparum, the causative agent of malaria, infects 500 million people a year, resulting in 2 million to 3 million deaths a year, while Trypanosoma brucei, Trypanosoma cruzi, and Leishmania species cause 20 million disease cases annually. The organism Toxoplasma gondii is the causative agent of AIDS-encephalitis.

The most common treatments for these parasitic diseases often cause adverse side effects, requiring a stoppage of treatment.

Drs. Roberto Docampo and Silvia Moreno, veterinary pathobiology, along with University of Illinois professor of chemistry and biophysics Dr. Eric Oldfield, led a team of eight Illinois researchers and others working at the Venezuelan Institute for Scientific Research in Caracas and the London School of Hygiene and Tropical Medicine. The work was published in the March 15, 2001, issue of the Journal of Medicinal Chemistry.

The bisphosphonate drugs are active against the causative agents of African sleeping sickness, Chagas’ disease, malaria, leishmaniasis, and toxoplasmosis, according to the findings. Drugs such as Merck’s Fosamax®, Procter & Gamble’s Actonel®, and Novartis’s Aredia® act much as they do in inhibiting bone resorption, by targeting and inhibiting a specific enzyme, farnesyl-pyrophsophate synthase, in the parasites.

The specificity is thought to be due in part to enhanced uptake into specialized granules called acidocalcisomes, which were discovered by Drs. Docampo and Moreno and are present in all of the parasitic cells. “These granules are chemically similar to bone,” Dr. Docampo says, “and we think this may contribute to drug uptake and selectivity.”

The National Institutes of Health, World Health Organization, Burroughs Wellcome Fund, Howard Hughes Medical Institutes, and the American Heart Association, Midwest, funded the work.

 

African wildlife databases benefit animal conservation efforts
The health and welfare of African lions, leopards, and cheetahs are coming into focus–in Illinois. What is being learned, researchers say, will help with the management of the threatened big cats in Africa, as well as those in zoos throughout the world.

“The government of Namibia has genuine concerns about how to best manage its animals,” said Dr. Michael J. Kinsel (DVM IL ’93) of the College’s Zoological Pathology Program. “These concerns are very important for the international wildlife community.”

Namibia sought help from Chicago’s Brookfield Zoo and the ZPP in 1994. A collaborative program has led to an unprecedented database of demographics, habitats, diseases, genetics and reproductive issues related to the lion.

Various samples (tissue, blood, serum, parasites, sperm, etc.) have been studied at the Chicago zoo and at the Veterinary Diagnostic Laboratory in Urbana. The samples are archived at the zoo.

The current effort, the Namibian Carnivore Monitoring Program, seeks to obtain the same information for leopards and cheetahs.

“A big question is what diseases affect leopards,” says Dr. Kinsel, who works from Loyola University near the zoo. “If you search the literature, you will come up with very little. Nor do we know much about the genetics of leopards. They are secretive animals. Namibia doesn’t know how many animals there are in the country, but there are populations that have been tracked for two years.”

Applying the approach to cheetahs is important. Namibia is home to 70 percent of the world’s cheetah population. “If we lose Namibia’s population, we will have essentially lost the cheetah, because populations elsewhere are smaller and isolated,” Dr. Kinsel says.

Comprehensive databases of the spotted hyena, African dog, and black-backed jackal are also planned. “If we can see the differences between free-ranging and captive animals, we can enhance management in both habitats,” says Dr. Kinsel, who with other members of the team travels to Namibia a couple of times a year for fieldwork and to train local workers to collect samples and perform necropsies.

 

Sunlight, PCB exposure enhance skin cancer chances
Sunlight and PCB exposure can hit you where you least expect it. The combination enhances the development of non-melanoma skin cancer on parts of the body not directly exposed to the sun, according to a study conducted by Dr. Rhian Cope, Dr. Larry Hansen, and others in the Department of Veterinary Biosciences.

“The statistical power of our experiments leads us to believe that our results likely underestimate the strength of our conclusions,” says Dr. Cope. “Because PCB-contaminated soil and sun exposure are both extremely common, we must look at this issue in humans.”

In the study, which used the hairless mouse model of humans with non-malignant skin cancer, a group of mice was exposed for 77 days to soil from a Southern Illinois landfill site contaminated with polychlorinated biphenyls and polychlorinated dibenzofurans, a PCB byproduct. Some of the mice were then exposed five days a week for 28 weeks to solar ultraviolet radiation.

The PCB-sunlight combination led to a rapid growth of non-melanoma tumors on the non-light-exposed undersides of the mice. The tumors were slow growing and did not turn into squamous cell carcinomas, thus demonstrating their low malignant potential. PCB-exposed mice kept out of the light did not develop such tumors.

By day 281, mice exposed to sunlight but not the contaminated soil had developed twice the number of skin tumors in light-exposed areas than had PCB- and light-exposed mice. The study also showed that PCB-exposed mice ate more and grew fatter, regardless of exposure to light.

It was believed that the PCB-PCDF-contaminated soil, which caused chloracne (an acne-like eruption associated with dioxin exposure), served as a sunscreen, at least during early stages of exposure to UV light, according to Dr. Cope.

“Our results were complex, but it was clear that tumor growth was dependent on whether or not an animal’s skin was irradiated,” Dr. Cope says. “The only time we saw tumors at any site was in the presence of UV irradiation. It was clear that UV light promotes the development of tumors at non-light-exposed sites that were probably initiated by exposure to PCBs and PCDFs.”

In 1998, according to the American Academy of Dermatology, there were up to 1.2 million reported cases of non-melanona skin cancers in the United States.

The soil used in the study came from the Sangamo Landfill on the Crab Orchard Wildlife Refuge and had a PCB content at least as high as some areas in Anniston, Ala., where for 40 years a Monsanto plant produced PCBs used to insulate electrical transformers.

“PCB contamination is a more widespread problem than most people realize,” Dr. Hansen says, noting that millions of dollars are being spent on clean-up projects on the Hudson River in the northeast and in the Anniston area. “Several industrial areas of Europe also are highly contaminated,” he says.

Drs. Kanjana Imsilp and Carla K. Morrow, veterinary biosciences graduate students, also worked on this study, which was funded by the American Cancer Society. Results were presented at the 40th annual meeting of the Society of Toxicology in Nashville, Tenn., in March. Dr. Hansen will present additional findings at a PCB workshop in Brno, Czech Republic, where he will chair a session on human exposure and health effects, including human exposure at Anniston.