OREGON STATE UNIVERSITY

college of veterinary medicine

Unwanted impact of antibiotics broader, more complex than previously known

CORVALLIS, Ore. – Researchers at Oregon State University have discovered that antibiotics have an impact on the microorganisms that live in an animal’s gut that’s more broad and complex than previously known.

The findings help to better explain some of the damage these medications can do, and set the stage for new ways to study and offset those impacts.

The work was published online in the journal Gut, in research supported by Oregon State University, the Medical Research Foundation of Oregon and the National Institutes of Health.

Researchers have known for some time that antibiotics can have unwanted side effects, especially in disrupting the natural and beneficial microbiota of the gastrointestinal system. But the new study helps explain in much more detail why that is happening, and also suggests that powerful, long-term antibiotic use can have even more far-reaching effects.

Scientists now suspect that antibiotic use, and especially overuse, can have unwanted effects on everything from the immune system to glucose metabolism, food absorption, obesity, stress and behavior.

The issues are rising in importance, since 40 percent of all adults and 70 percent of all children take one or more antibiotics every year, not to mention their use in billions of food animals. Although when used properly antibiotics can help treat life-threatening bacterial infections, more than 10 percent of people who receive the medications can suffer from adverse side effects.

“Just in the past decade a whole new universe has opened up about the far-reaching effects of antibiotic use, and now we’re exploring it,” said Andrey Morgun, an assistant professor in the OSU College of Pharmacy. “The study of microbiota is just exploding. Nothing we find would surprise me at this point.”

This research used a “cocktail” of four antibiotics frequently given to laboratory animals, and studied the impacts.

“Prior to this most people thought antibiotics only depleted microbiota and diminished several important immune functions that take place in the gut,” Morgun said. “Actually that’s only about one-third of the picture. They also kill intestinal epithelium. Destruction of the intestinal epithelium is important because this is the site of nutrient absorption, part of our immune system and it has other biological functions that play a role in human health.”

The research also found that antibiotics and antibiotic-resistant microbes caused significant changes in mitochondrial function, which in turn can lead to more epithelial cell death. That antibiotics have special impacts on the mitochondria of cells is both important and interesting, said Morgun, who was a co-leader of this study with Dr. Natalia Shulzhenko, a researcher in the OSU College of Veterinary Medicine who has an M.D. from Kharkiv Medical University.

Mitochondria plays a major role in cell signaling, growth and energy production, and for good health they need to function properly.

But the relationship of antibiotics to mitochondria may go back a long way. In evolution, mitochondria descended from bacteria, which were some of the earliest life forms, and different bacteria competed with each other for survival. That an antibiotic would still selectively attack the portion of a cell that most closely resembles bacteria may be a throwback to that ingrained sense of competition and the very evolution of life.

Morgun and Schulzhenko’s research group also found that one of the genes affected by antibiotic treatment is critical to the communication between the host and microbe.

“When the host microbe communication system gets out of balance it can lead to a chain of seemingly unrelated problems,” Morgun said.

Digestive dysfunction is near the top of the list, with antibiotic use linked to such issues as diarrhea and ulcerative colitis. But new research is also finding links to obesity, food absorption, depression, immune function, sepsis, allergies and asthma.

This research also developed a new bioinformatics approach named “transkingdom network interrogation” to studying microbiota, which could help further speed the study of any alterations of host microbiota interactions and antibiotic impact. This could aid the search for new probiotics to help offset antibiotic effects, and conceivably lead to systems that would diagnose a person’s microbiome, identify deficiencies and then address them in a precise and individual way. 

Healthy microbiota may also be another way to address growing problems with antibiotic resistance, Morgun said. Instead of trying to kill the “bad” bacteria causing an illness, a healthy and functioning microbiota may be able to outcompete the unwanted microbes and improve immune function.

Collaborators on this research were from the OSU College of Pharmacy; OSU College of Veterinary Medicine; OSU College of Science; the National Cancer Institute; University of British Columbia; University of Maryland School of Medicine; and the National Institutes of Health.

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Andrey Morgun, 541-737-8047

Deworming programs in animal, human populations may have unwanted impacts

CORVALLIS, Ore. – A study of the effects of worming medications on infectious disease in wildlife herds showed an unexpected and alarming result – although it helped reduce individual deaths from a bovine tuberculosis infection, it hugely increased the potential for spread of the disease to other animals.

The findings, from one of the first field studies ever done on this issue, will be published Friday in the journal Science.

They were contrary to expectations based on laboratory studies, and suggest the possibility that broad use of medical treatments such as this can backfire. They may actually increase the problem with diseases they were meant to reduce.

Both in animals and possibly human disease, treatments that aid an individual could come at the expense of a wider spread of disease in the larger community, the research suggested.

“This study indicates that we need to better understand how some medical treatments affect other health issues, in particular infectious disease,” said Anna Jolles, an epidemiologist at Oregon State University and co-author of the study, along with Vanessa Ezenwa at the University of Georgia.

The research, supported by the National Science Foundation, was done with more than 200 animals in two herds of free-ranging African buffalo in Kruger National Park in South Africa. Half were given deworming medication and the others not.

It was known that infection with parasitic helminth worms can decrease the effective immune response against some infectious diseases, in this case bovine tuberculosis, which is common among these animals. Scientists expected the worming medications to save lives while reducing the risk of infection and disease progression.

They found that deworming treatments did improve the survival of animals infected with bovine tuberculosis – in fact, dewormed animals with tuberculosis survived just as well as TB-free animals. However, deworming did not reduce the risk of new infections, and there was a dramatic eight-fold increase in the number of buffalos that an infected animal could potentially infect – a reference to the “R-nought,” or reproductive multiplier that epidemiologists use to predict the potential for spread of infection in a community.

A buffalo with bovine tuberculosis but no worm treatments has, on average, the potential to infect about one other buffalo. This study found that after worm treatment, a buffalo with this disease had the theoretical potential to infect nine other buffalos. This difference was based on the finding that dewormed buffalo with TB can survive for years, whereas the life expectancy of untreated TB-infected buffalo was much shorter.

These issues are of significant concern not just for animal, but also human health, researchers say.

Helminth worm infections are among the most ubiquitous parasites on Earth, infecting 1 billion people and causing significant losses among both livestock and wildlife. Other studies have linked co-infection with these worms to increased risk of death from both tuberculosis and HIV/AIDS in human patients, largely due to their ability to reduce and otherwise skew the natural immune response to both viral and bacterial infection.

This is a larger problem in the developing world, and some major deworming programs in human populations are already in place due to the range of health concerns posed by the parasites. It’s believed that mass deworming programs may reduce overall deaths from some of the major killers in such areas, such as malaria, tuberculosis and HIV infection.

“These results are pretty alarming,” said Jolles, who is a researcher in both the OSU College of Science and College of Veterinary Medicine.

“We expected deworming effects to be all positive, both for individual buffalo, and in terms of reducing disease spread,” Jolles said. “But what we found is positive effects for individual animals, but potentially much faster disease spread at the population level.”

From these results in buffalo, Jolles said, one should not to jump to conclusions about changing deworming treatments in people. But they do raise questions about large, broad-based public deworming programs.

“We must pay attention to health problems that may increase as a result of the program, as well as problems that we are solving,” she said.

The findings also raise questions about aspects of animal agriculture, Jolles said, especially in developing countries. It may be important to match deworming programs with vaccines for infectious disease and other treatments to ensure that the overall health of the herd is protected.

The potential to actually increase spread of a disease following a health treatment such as deworming may vary widely, Jolles said, with different animal species and different infectious diseases.

More studies are urgently needed to address the primary question raised by this research, the scientists said. On a community level, will large-scale deworming treatments alleviate, or will they exacerbate the health impacts of other, sometimes deadly infections?

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Anna Jolles, 541-737-4719

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African buffalo

African buffalo

“Glowing” new nanotechnology guides cancer surgery, also kills remaining malignant cells

CORVALLIS, Ore. – Researchers at Oregon State University have developed a new way to selectively  insert compounds into cancer cells - a system that will help surgeons identify malignant tissues and then, in combination with phototherapy, kill any remaining cancer cells after a tumor is removed.

It’s about as simple as, “If it glows, cut it out.” And if a few malignant cells remain, they’ll soon die.

The findings, published in the journal Nanoscale, have shown remarkable success in laboratory animals. The concept should allow more accurate surgical removal of solid tumors at the same time it eradicates any remaining cancer cells. In laboratory tests, it completely prevented cancer recurrence after phototherapy.

Technology such as this, scientists said, may have a promising future in the identification and surgical removal of malignant tumors, as well as using near-infrared light therapies that can kill remaining cancer cells, both by mild heating of them and generating reactive oxygen species that can also kill them.

“This is kind of a double attack that could significantly improve the success of cancer surgeries,” said Oleh Taratula, an assistant professor in the OSU College of Pharmacy.

“With this approach, cancerous cells and tumors will literally glow and fluoresce when exposed to near-infrared light, giving the surgeon a precise guide about what to remove,” Taratula said. “That same light will activate compounds in the cancer cells that will kill any malignant cells that remain. It’s an exciting new approach to help surgery succeed.”

The work is based on the use of a known compound called naphthalocyanine, which has some unusual properties when exposed to near-infrared light. It can make a cell glow as a guide to surgeons; heat the cell to kill it; and produce reactive oxygen species that can also kill it. And by adjusting the intensity of the light, the action of the compound can be controlled and optimized to kill just the tumor and cancer cells. This research was done with ovarian cancer cells.

However, naphthalocyanine isn’t water soluble and also tends to clump up, or aggregate, inside the body, in the process losing its ability to makes cells glow and generate reactive oxygen species. This also makes it difficult or impossible to find its way through the circulatory system and take up residence only in cancer cells.

OSU experts overcame these problems by use of a special water-soluble polymer, called a dendrimer, which allows the napthalocyanine to hide within a molecule that will attach specifically to cancer cells, and not healthy tissue. The dendrimer, an extremely tiny nanoparticle, takes advantage of certain physical characteristics that blood vessels leading to cancer cells have, but healthy ones do not. It will slip easily into a tumor but largely spare any healthy tissue.

Once in place, and exposed to the type of light needed, the cancer cells then will glow – creating a biological road map for a surgeon to follow in identifying what tissues to remove and what to leave. At the same time, a few minutes of this light exposure activate the naphthalocyanine to kill any remaining cells.

This one-two punch of surgery and a nontoxic, combinatorial phototherapy holds significant promise, Taratula said. It’s quite different from existing chemotherapies and radiotherapies.

“For many cancers, surgery is a first choice of treatment,” Taratula said. “In coming years we may have a tool to make that surgery more precise, effective and thorough than it’s been before.”

Before attempting human clinical tests, OSU researchers hope to perfect the process and then collaborate with Shay Bracha, an assistant professor in the OSU College of Veterinary Medicine, to test it on live dogs that have malignant tumors. The technique has already been shown successful in laboratory mice. Worth noting, the researchers said, is that even as phototherapy was destroying their malignant tumors, the mice showed no apparent side effects and the animals lost no weight.  

Systems with technology similar to this are also being tested by other researchers, but some of them require several imaging and therapeutic agents, repeated irradiation and two lasers. This increases cost, may lessen effectiveness and increase risk of side effects, OSU researchers said in their report.

This research was supported by the OSU College of Pharmacy, the Medical Research Foundation of Oregon and the PhRMA Foundation.

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Oleh Taratula, 541-737-5785

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Phototherapy system

Biomarker could provide early warning of kidney disease in cats

CORVALLIS, Ore. – Researchers from Oregon State University and other institutions have developed a new biomarker called “SDMA” that can provide earlier identification of chronic kidney disease in cats, which is one of the leading causes of their death.

A new test based on this biomarker, when commercialized, should help pet owners and their veterinarians watch for this problem through periodic checkups, and treat it with diet or other therapies to help add months or years to their pet’s life.

Special diets have been shown to slow the progression of this disease once it’s identified.

The findings were made in a controlled study of 32 healthy, but older cats, and have been published in The Veterinary Journal by researchers from OSU and IDEXX Laboratories. They demonstrated the efficacy of a biomarker that could form the basis for a new diagnostic test.

“Chronic kidney disease is common in geriatric cats and often causes their death,” said Jean Hall, a small animal medical expert and professor in the OSU College of Veterinary Medicine. “Damage from it is irreversible, but this is an important advance, in that we should be able to identify the problem earlier and use special diets to slow the disease.”

Many of these same health issues also relate to older dogs, and in continued research scientists believe they may make similar findings.

Renal decline is normal in most cats, experts say, as they reach 12-18 years of age, and along with issues such as cancer and gastrointestinal disease is one of the more common causes of death. But studies have shown that the problem can also be managed with special foods that reduce protein and phosphorus, while adding fish oil, antioxidants, L-carnitine and medium-chain triglycerides.

This biomarker was able to identify the onset of kidney disease in cats on average 17 months earlier than any existing approach, and in at least one case four years earlier. With special diets and care, some cats have lived several years after the disease was diagnosed.

The only existing test for the disease, which has been used for decades, is a blood test that checks creatinine levels, a marker of the breakdown of muscle protein. However, cats lose lean body mass as they age, so creatinine levels may be normal.  SDMA is not influenced by lean body mass and thus more accurately diagnoses the loss of kidney function, even if lean body mass has decreased.

The early symptoms of this disease are fairly non-specific, such as loss of appetite, weight loss, or vomiting.

The cats in this research were housed at the Science and Technology Center of Hill’s Pet Nutrition Inc.  The company provided data and samples for analysis in order to better understand the dietary needs of cats with early renal disease, and initiated the study to investigate how best to lengthen and enrich the lives of cats with the condition.

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Jean Hall, 541-737-6537

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Aging cat
Aging cat

Virulent bacteria affecting oysters found to be a case of mistaken identity

CORVALLIS, Ore. -  The bacteria that helped cause the near-ruin of two large oyster hatcheries in the Pacific Northwest have been mistakenly identified for years, researchers say in a recent report.

In addition, the study shows that the bacteria now believed to have participated in that problem are even more widespread and deadly than the previous suspect.

Although the hatchery industry has largely recovered, primarily by better control of ocean water acidity that was also part of the problem, the bacterial pathogens remain a significant concern for wild oysters along the coast, researchers said.

For many years, it had been believed that the primary bacteria causing oyster larval death in the Pacific Northwest was Vibrio tubiashii. Now, scientists say that most, or possibly all of the bacterial problem was caused by a different pathogen, Vibrio coralliilyticus, a close cousin that’s now known to be even more virulent to Pacific oysters.

The findings were published in Applied and Environmental Microbiology, by researchers from the College of Veterinary Medicine at Oregon State University, the U.S. Department of Agriculture, and Rutgers University. The research was supported by the USDA.

“These bacteria are very similar, they’re close cousins,” said Claudia Häse, an OSU associate professor and expert in microbial pathogenesis. “V. coralliilyticus was believed to primarily infect warm water corals and contributes to coral bleaching around the world. It shares some gene sequences with V. tubiashii, but when we finally were able to compare the entire genomes, it became apparent that most of what we’re dealing with in the Pacific Northwest is V. coralliilyticus.”

Scientists now say that V. coralliilyticus is not only far more widespread than previously believed, but that it can infect a variety of fish, shellfish and oysters, including rainbow trout and larval brine shrimp. And it appears to be the primary offender in bacterial attacks on Pacific Northwest oyster larvae.

OSU experts have developed a rapid diagnostic assay for this bacteria that is nearing commercialization, and it may help assess problems both in oyster and coral health, Häse said.

“Although we’ve largely addressed the problems the hatcheries face, these bacteria continue to pose threats to wild oysters,” Häse said. “And corals are still declining in many places, the Great Barrier Reef in Australia is dying at an alarming rate. Better diagnostics might help in all of these situations.”

In what’s now understood to be a problem with multiple causes, these pathogenic bacteria were involved in major crashes of oyster hatcheries, causing shortages in seed oysters for commercial producers. Dramatic losses were suffered in a Netarts Bay, Oregon, hatchery in 2005, and Washington hatcheries were also hard hit. Bacterial infection, water acidity, oxygen depletion and rising seawater temperatures are all believed to have been part of the problem.

By better monitoring and control of water acidity, which was one serious concern, hatcheries have been able to regain most of their productive capabilities. Wild oysters, however, continue to face the multiple pressures from rising acidity, pathogenic bacteria and other forces that have led to serious hatchery mortality.

Those problems have not been made any easier by the lack of funding for identification and studies of the bacteria that researchers now know to be causing infection.

In laboratory tests, strains of V. tubiashii did not show significant pathogenicity to Pacific oysters. V. coralliilyticus, by contrast, is highly infectious to both Pacific and Eastern oyster larvae, and perhaps other shellfish species.

“The Vibrio genus and many bacteria associated with it are a huge problem in fish and shellfish aquaculture, and we should be studying them more aggressively,” Häse said. “V. coralliilyticus, in particular, has a very powerful toxin delivery system, and vibrios are some of the smartest of all bacteria. They can smell, sense things and swim toward a host.”

It’s believed that increasing environmental stresses may make oysters and other marine life more vulnerable to these types of bacterial infection, researchers say.

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Claudia Häse, 541-737-7001

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Oyster larvae

Hygienic funerals, better protection for health workers offer best chance to stop Ebola

CORVALLIS, Ore. – Hygienic funeral practices, case isolation, contact tracing with quarantines, and better protection for health care workers are the keys to stopping the Ebola epidemic that continues to expand in West Africa, researchers said today in a new report in the journal Science.

Continuing the status quo of intervention efforts that were in place as of Sept. 19 would allow continued expansion of the epidemic by about 224 new cases daily in Liberia by Dec. 1, and 348 new daily cases by Dec. 30, the scientists reported in their analysis.

However, they said broad implementation “with utmost urgency” of more aggressive approaches they recommended, used at a reasonably high level of efficiency, could by mid-March lead to its control in Liberia, the focal point of the epidemic.

Researchers from Yale University, Oregon State University, and the Ministry of Health and Social Welfare in Liberia concluded that funerals, as they have been customarily practiced in this region, were what they called “super-spreader events” that have had a disproportionate impact on the early transmission of the virus.

Changes in those practices are the single most important, practical step that could help place the number of new Ebola infections on a downward path. But a whole suite of actions are needed, they cautioned, and reducing transmission in hospitals and the community will not by itself bring the epidemic under control.

“The cultural body preparation and funeral practices that are common in West Africa have driven the initial spread of this disease,” said Jan Medlock, an assistant professor in the OSU Department of Biomedical Sciences and an expert in mathematical epidemiology and evolution of infectious disease.

“These funeral practices often included washing, touching and kissing of bodies that were still capable of spreading the Ebola virus,” Medlock said. “It is imperative that funeral transmission be stopped, and also that we take other aggressive steps to isolate cases and better protect health care workers.”

The findings were made with complex mathematical models that consider many variables in how the disease is spreading, what steps are being taken to slow its progression and how effective those steps are. The research sought to identify not only what would theoretically work, but what was most practical and achievable.

The goal, the researchers said, should be to shift the current Ebola epidemic from one that is expanding to one that is slowly declining – to change what scientists call the “basic reproductive number” to less than 1, so the epidemic is on the road to ultimate extinction. They estimated that in Liberia the Ebola reproductive number is currently 1.63, meaning that two infected people would infect, on average, about three more people, and the epidemic continues to expand.

Getting that reproductive number below 1 will require adequate and proper use of personal protective equipment, more complete case isolations, contact precautions, quarantines, and particularly improved funeral practices. Achieving these goals at a success rate of about 60 percent could ultimately curtail the epidemic, the researchers said.

To arrive at their conclusions, the scientists used mathematical analysis to consider such factors as the density of infected and uninfected people in an area, numbers attending a funeral, those hospitalized, their relatives, health care workers in the hospital, and the general community.

Instead of traditional burial preparations, the researchers endorsed a very hygienic approach that includes disinfecting the cadaver before placing it in a plastic body bag and doing further disinfecting. Human-to-human transmission of Ebola occurs mostly through direct or indirect contact with body fluids, the researchers noted in their report, and deceased victims still carry a high viral load in their blood and excretions.

Another significant concern, the researchers said, is under-reporting of cases, both in hospitals and the general community. This could slow the stoppage of the epidemic and increase the level of intervention needed to stop it.

Other things could also change as the epidemic evolves. Funeral attendance and traditional burial practices may decline as awareness builds about the disease, but contacting people who may have been exposed could become even more difficult as people move from urban to rural areas.

This study was supported by the National Institutes of Health and the Notsew Orm Sands Foundation. It was a collaboration of researchers from the OSU College of Veterinary Medicine, the Yale School of Public Health and the Ministry of Health and Social Welfare in Liberia. The corresponding author was Alison Galvani at the Yale School of Public Health. It is being published in the journal Science at its online Science Express web site.

The findings of this study were specific to Liberia but should have some relevance to other places with similar cultural practices or approaches to disease management, Medlock said. They are less relevant in situations where the disease has spread beyond Africa into the United States, Europe and other parts of the developed world, he said, where aggressive isolation and containment of infected people or quarantine of those exposed is more practical.

Given the magnitude of this health crisis, it’s already apparent that Ebola poses an international threat that requires an international response and aid, the scientists said in their conclusion.

“Ebola poses an urgent threat not only to West Africa but also to the international community,” they wrote.

“The implementation of effective interventions needed to reverse the growth of the Ebola outbreak in impoverished West African countries will be logistically challenging even with substantial international aid, but impossible without it.”

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Jan Medlock, 541-737-6874

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Jan Medlock
Jan Medlock

Compound from hops aids cognitive function in young animals

CORVALLIS, Ore. – Xanthohumol, a type of flavonoid found in hops and beer, has been shown in a new study to improve cognitive function in young mice, but not in older animals.

The research was just published in Behavioral Brain Research by scientists from the Linus Pauling Institute and College of Veterinary Medicine at Oregon State University. It’s another step toward understanding, and ultimately reducing the degradation of memory that happens with age in many mammalian species, including humans.

Flavonoids are compounds found in plants that often give them their color. The study of them – whether in blueberries, dark chocolate or red wine - has increased in recent years due to their apparent nutritional benefits, on issues ranging from cancer to inflammation or cardiovascular disease. Several have also been shown to be important in cognition.

Xanthohumol has been of particular interest because of possible value in treating metabolic syndrome, a condition associated with obesity, high blood pressure and other concerns, including age-related deficits in memory. The compound has been used successfully to lower body weight and blood sugar in a rat model of obesity.

The new research studied use of xanthohumol in high dosages, far beyond what could be obtained just by diet. At least in young animals, it appeared to enhance their ability to adapt to changes in the environment. This cognitive flexibility was tested with a special type of maze designed for that purpose.

“Our goal was to determine whether xanthohumol could affect a process we call palmitoylation, which is a normal biological process but in older animals may become harmful,” said Daniel Zamzow, a former OSU doctoral student and now a lecturer at the University of Wisconsin/Rock County.

“Xanthohumol can speed the metabolism, reduce fatty acids in the liver and, at least with young mice, appeared to improve their cognitive flexibility, or higher level thinking,” Zamzow said. “Unfortunately it did not reduce palmitoylation in older mice, or improve their learning or cognitive performance, at least in the amounts of the compound we gave them.”

Kathy Magnusson, a professor in the OSU Department of Biomedical Sciences, principal investigator with the Linus Pauling Institute and corresponding author on this study, said that xanthohumol continues to be of significant interest for its biological properties, as are many other flavonoids.

“This flavonoid and others may have a function in the optimal ability to form memories,” Magnusson said. “Part of what this study seems to be suggesting is that it’s important to begin early in life to gain the full benefits of healthy nutrition.”

It’s also important to note, Magnusson said, that the levels of xanthohumol used in this study were only possible with supplements. As a fairly rare micronutrient, the only normal dietary source of it would be through the hops used in making beer, and “a human would have to drink 2000 liters of beer a day to reach the xanthohumol levels we used in this research.”

In this and other research, Magnusson’s research has primarily focused on two subunits of the NMDA receptor, called GluN1 and GluN2B. Their decline with age appears to be related to the decreased ability to form and quickly recall memories.

In humans, many adults start to experience deficits in memory around the age of 50, and some aspects of cognition begin to decline around age 40, the researchers noted in their report.

This research was supported by the National Institutes of Health.

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Hops

Hops

Use of dengue vaccine may cause short-term spikes in its prevalence

CORVALLIS, Ore. – As researchers continue to work toward vaccines for serious tropical diseases such as dengue fever, experts caution in a new report that such vaccines will probably cause temporary but significant spikes in the disease in the years after they are first used.

This counter-intuitive and unwanted result could lead to frustrated policy makers, a skeptical public and concerns that the vaccine is making things worse instead of better, researchers say.

In fact, it will just be the natural result of complex interactions between less-than-perfect vaccine protection and routine fluctuations in the populations of insects who carry the diseases.

“Our analysis suggests that if we develop and widely use a vaccine for dengue fever, there may later be spikes in the incidence of the disease that are two to three times higher than its normal level,” said Jan Medlock, an assistant professor in the Department of Biomedical Sciences at Oregon State University, and expert on the evolution and epidemiology of infectious disease.

“We can explain why this will happen and show how, in the long run, vaccine use will clearly result in fewer cases of disease,” Medlock said. “Our concern is to warn people in advance about this issue, so that policy makers and the public don’t freak out and lose faith in the vaccination programs.”

This research, published in Epidemiology and Infection, was done by experts at the OSU College of Veterinary Medicine and Clemson University, both of which supported the studies. Scientists used mathematical modeling to examine the quirks of infectious disease transmission that may lead to this quandary. The work was specific to dengue fever, but may also be relevant to other diseases for which vaccines are being sought, such as malaria, and in which the level of protection is less than total.

Dengue fever is a serious illness that affects about 50 million people a year, and for which researchers are hoping to develop effective vaccines in the near future. It’s not usually fatal but is extremely common in the tropics and subtropics, and has re-emerged in recent decades as the use of insecticides such as DDT has been stopped.

There are several serotypes, or strains of the dengue virus, that are spread by mosquitoes. One infection provides some protection, and two infections usually make a person resistant for the rest of their life. In Thailand, where the disease is prevalent, about 80 percent of children have two infections by the age of 11 and develop resistance. Dengue fever is found in 100 countries around the world and 2.5 billion people are at risk of infection.

“The problem, if and when we develop and use a vaccine, is that it will provide some, but not complete protection, and it will interrupt the natural, fairly steady rate of infections among children,” Medlock said.

In this scenario, the beginning of a vaccination program will slow the numbers of children getting the disease – for a while. But it’s expected that a dengue vaccine will not provide total protection against infection. Then, during a period when naturally fluctuating mosquito populations reach an unusually high level, a disproportionate number of children – who are still vulnerable to infection and have never had the disease – will become infected in a short period.

This could cause loss of faith in the vaccination program among the public or policy makers who have never seen such high levels of the disease, stretch the capabilities of health care facilities and workers to care for the sick, and in a worst-case scenario lead people to avoid the vaccine, researchers said. Some short-term spikes could even be as high as seven times the average rate, they said.

“In fact, we conclude in this analysis that over a 15-year period, a vaccination program will clearly reduce the number of overall infections,” Medlock said. “These significant spikes will mostly occur as the program is beginning. What we need to do is help people understand these forces so they anticipate them.”

A possible way to deal with this phenomenon, researchers said, is literally to vaccinate fewer people. This would cause higher numbers of people to get the disease in the long run but reduce the intensity of the spikes and the associated demands on a health care system.

The levels of disease will fluctuate based on such variables as location, climate, the efficacy of a vaccine, the numbers of people vaccinated, surges in insect populations, and other factors. This phenomenon may have occurred, or may occur in the future, with almost any vaccine that provides partial, but not total protection against infection.

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Research could lead to new cancer assay, aid both dogs and humans

CORVALLIS, Ore. – Veterinary researchers at Oregon State University have identified a unique group of proteins that indicate the presence of transitional cell carcinoma – the most common cause of bladder cancer – and may lead to a new assay which could better diagnose this disease in both dogs and humans.

Bladder cancer is particularly common in some dog breeds, such as collies, sheepdogs and terriers, but is rarely diagnosed in animals before it has spread significantly. Some assays exist to detect it in humans, but they often have a high-number of false-positive identifications.

An improved assay to detect this serious disease much earlier in both animals and humans should be possible, scientists said, and may even become affordable enough that it could be used as an over-the-counter product to test urine, much like a human pregnancy test. Some of the work may also contribute to new therapies, they said.

“Research of this type should first help us develop a reliable assay for this cancer in dogs, and improve the chance the disease can be caught early enough that treatments are effective,” said Shay Bracha, an assistant professor in the OSU College of Veterinary Medicine.

“However, this type of cancer is essentially the same in dogs and humans,” Bracha said. “Dogs are an excellent model for human cancer research, and an assay that works with dogs should be directly relevant to creation of a similar assay for humans. We hope to make it inexpensive and convenient, something that people could use routinely to protect either the health of their pets or themselves.”

The findings were published recently in Analytical Chemistry, a professional journal.

In this research, scientists used mass spectrometry and the evolving science of proteomics to identify 96 proteins that appear related to transitional cell carcinoma. This is a fairly common cancer in dogs, often as a result of exposure to pesticides, herbicides, and poor quality foods; and in humans is closely related to smoking.

Advanced-stage disease in both dogs and humans has a poor prognosis, as chemotherapy and radiation treatments are often ineffective. Average survival time is less than one year. Some assays exist to help identify the disease in humans but can produce false positive results, often as a result of urinary tract infections. And the biopsies used to make a definitive diagnosis require general anesthesia and also run the risk of actually spreading the disease.

The group of proteins identified in this research already have a 90 percent accuracy, and researchers say they hope to improve upon that with continued research.

However, researchers say that some of these proteins are more than just biomarkers of the disease – they are part of the disease process. Identifying proteins that are integral to the spread of the cancer may allow new targets for intervention and cancer therapies, they said.

Collaborators on this research included the OSU Department of Chemistry. A mathematical model that was integral to the study was created by Jan Medlock, an OSU assistant professor of veterinary medicine, and veterinary researchers Michael McNamara and Ian Hilgart helped initiate the project. The work was supported in part by the National Institutes of Health.

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Shay Bracha, 541-737-4844

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Border collie

OSU assisting in alpaca rescue operation

CORVALLIS, Ore. - The last of about 175 imperiled alpacas that are being removed from a farm near Falls City, Ore., will arrive today or early this week at Oregon State University as part of a continuing rescue operation to help care for and save the lives of these animals.

Transport began late last week but only 54 got through, and operations had to be suspended due to the heavy winter storm, a traffic accident and difficult travel conditions. A team of doctors and veterinary students at OSU will now work with the incoming animals to assess their health, do necessary procedures, improve their nutritional status and aid their recovery.

Owners of the ranch that had housed the alpacas are facing legal charges in Polk County. Meanwhile, the College of Veterinary Medicine has volunteered its facilities to help continue the rescue operation that was begun by the Polk County Sheriff’s Department and Cross Creek Alpaca Rescue volunteers.

Ultimately, all of the animals will be made available for adoption, officials said.

“The OSU College of Veterinary Medicine is one of the few agencies in Oregon that has the ability and expertise to manage an operation of this size,” said Helen Diggs, a professor of veterinary medicine and director of the OSU Laboratory Animal Resources Center. “The Research Office at OSU has also made it clear that we will do what we can to help with this difficult situation.”

Although travel is still difficult, officials hope that most of the remaining alpacas will arrive today or early this week at the Research Animal Isolation Laboratory, one of the campus facilities large enough to handle so many animals at once. Some with special needs are also being treated in the large animal hospital in Magruder Hall on the OSU campus.

“Many of these animals are very thin and we’ve been told that a substantial number have already died,” said Chris Cebra, a professor of large animal internal medicine in the College of Veterinary Medicine, and an expert in the treatment of camelids such as llamas and alpacas.

“From what we’ve seen, we’ll be dealing with malnutrition, heavy parasite loads, some pregnant animals, newborns, and various health conditions,” Cebra said. “We’ll continue to feed the animals, assess and treat medical conditions, check vaccination status, and generally improve their quality of life and suitability for a new home.”

Given the unusually large influx of animals at one time, a number of supervised veterinary students will also work in the rescue operation, allowing them a substantial amount of hands-on training while helping veterinary doctors more quickly and effectively give the entire herd the treatment it needs.

Once the alpacas recover their health, adoption will be possible from the Polk County Sheriff’s Office, which is working with Cross Creek Alpaca Rescue to identify suitable placements. Initial inquiries for adopting one or more of the animals may be directed to Cross Creek Alpaca Rescue, at http://www.crosscreekalpacarescue.org/.

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Helen Diggs, 541-737-6213

 

Chris Cebra, 541-737-4456

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Alpaca needs care


Alpacas being fed

Alpacas being fed