April 3, 2009
NIH Podcast Episode #0081
Balintfy: Welcome to the 81st episode of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health—the nation's medical research agency. I'm your host Joe Balintfy. Coming up in this episode, news on a couple of surveys, one about teen drug use, the other on alternative medicine practices. Also, part two of our series on the study of proteins. But first a report on the connection between ozone and breathing troubles. That's next on NIH Research Radio.
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Research Finds New Cause of Ozone Wheezing and Potential Treatments
Balintfy: Ozone is a common urban air pollutant. Estimates from Environmental Protection Agency analysis, show that ozone costs the United States about five billion dollars a year as a result of premature deaths, hospitalizations and school absences. Inhalation of ozone can lead to irritation of the airways—breathing passages—and increased wheezing, particularly in children and adults who have asthma and chronic obstructive lung disease. Now, researchers have discovered a cause of airway irritation and wheezing after exposure to ozone. These findings help identify potential new targets for drugs which may eventually help physicians better treat emergency room patients suffering from wheezing, coughing and shortness of breath. Dr. Stavros Garntziotis is a principal investigator at the National Institute of Environmental Health Sciences.
Garantziotis: The connection between ozone and the mechanism that leads to wheezing and airway irritation has not been very clear. And what we have found using a mouse model is that the connection may actually have to do with a naturally occurring sugar in the body which is called hyaluronan.
Balintfy: Dr. Garantziotis explains that it is not ozone itself that causes the body to wheeze, but the way the lungs respond to ozone.
Garantziotis: Now, as I’ve said, hyaluronan is a naturally occurring sugar, only in a healthy person it’s usually found in a long–chain form. So it’s occurring in long chains. What we have found if we expose mice to ozone to similar concentrations that would, for example, be found or a person would be exposed in a high ozone day, we find much more hyaluronan in the airways. But even more importantly, we find that instead of the long–chain hyaluronan, we find a short–chain hyaluronan. That seems to be directly causing airway hyper–responsiveness, meaning irritability of airways and the equivalent of wheezing, in other words.
Balintfy: Dr. Garantziotis adds that there are at least two ways that these findings could potentially lead to treatment options for the patients that have been exposed to ozone and have shortness of breath symptoms.
Garantziotis: For one, we could bind hyaluronan away using a hyaluronan–binding protein and that completely abolished the airway hyper–responsiveness and airway irritation. We also were able to give the long–chain—the naturally occurring hyaluronan, if you will—as a competitor, and that seemed to counteract the effects that we observed after ozone exposure.
Balintfy: Ozone is formed in the inner atmosphere in the presence of sunlight from pollutants emitted from vehicles and other sources. Exposure occurs when people inhale air containing ozone. For details on this study, visit www.niehs.nih.gov.
Downward Trend in Teen Marijuana Use Slows; Prescription Drug Abuse Remains High
Balintfy: Now some surveys from the NIH. First, there are signs that the ongoing decline in teen marijuana use in recent years has stalled; however the downward trend in cigarette and alcohol use continues. This is according to the 2008 Monitoring the Future Survey. The survey—now in its 33rd year—indicates that marijuana use among eighth–, tenth–, and twelfth–graders, which has shown a consistent decline since the mid–1990s, appears to have leveled off. But roughly 11 percent of eighth graders, 24 percent of tenth graders, and 33 percent of twelfth graders still reported marijuana use in the past year.
Volkow: These are still very unacceptably high numbers.
Balintfy: Dr. Nora Volkow is the director of the National Institute on Drug Abuse.
Volkow: Because a significant portion of high school students take marijuana. And it’s also one of the drugs that then predicts utilization of other types of drugs.
Balintfy: The 2008 Monitoring the Future survey also shows a continuing high rate of prescription drug abuse among teens, with little change seen in the past six years. Nearly 10 percent of seniors reported past year nonmedical use of Vicodin, and 4.7 percent report abusing Oxycontin. Both are powerful opioid painkillers. Dr. Volkow points out that seven of the top 10 drugs abused by twelfth graders in the year prior to the survey, were prescribed or purchased over–the–counter.
Volkow: We have not been able to make a dent in the pattern of the use of these drugs. Even though in the past five years we’ve seen significant decreases, that is not the case for prescription medications.
Balintfy: There are some bright spots in the survey—among them, that cigarette smoking is at the lowest rate in the history of the survey. And there continues to be a gradual decline in alcohol use in all grades.
Volkow: Still—so this is very good news—but still, the rate of smoking which is ten percent in tenth graders, daily smoking, and the rate of drinking behavior, which is 25 percent, regular drinking behavior, is unacceptably high. So you can take it both ways: It’s very good news, vis–à–vis the patters the trends, but it’s still not a situation where we can become complacent. We still have a lot of prevention work to do.
Balintfy: Dr. Volkow reminds that tobacco and alcohol use by teens has devastating related heath costs. Experts are also concerned by what they see as softening of attitudes about some drugs: In particular a continuing decline among twelfth graders who perceive use of LSD as harmful. Similarly, the proportion of eighth graders who perceive inhalants as harmful has declined, as has their disapproval of inhalant abuse. For more on the survey and the dangers of teen drug abuse, visit www.nida.nih.gov.
Survey Shows Promise in Usage of Complementary and Alternative Medicine in Children and Adults
Balintfy: From NIDA to NCCAM, another survey shows results on use of complementary and alternative medicine. Wally Akinso has the story.
Akinso: A new government survey found that 38 percent of adults and 12 percent of children use complementary and alternative medicine, which is a group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine. Dr. Josephine Briggs, Director of the National Center for Complementary and Alternative Medicine, says the survey provides the most current, comprehensive, and reliable source of information on Americans’ use of complementary and alternative medicine.
Briggs: We found that many Americans are turning in pursuit of better health to practices like the use of herbs, acupuncture, yoga, meditation, message and chiropractic or osteopathic manipulation. These approaches are used for many health problems but most particularly for chronic pain.
Akinso: Dr. Briggs explains NCCAM’s effort to support complementary and alternative medicine research.
Briggs: We are working hard to support research that will help us understand better the optimal role of complementary and alternative interventions. The data also highlight the importance of patients and doctors, talking about complementary and alternative medicine use.
Akinso: Dr. Briggs added that future analyses of the survey’s data may help explain some of the observed variation in the use of individual complementary and alternative medicine therapies and provide great insights into usage patterns among Americans. For more information on the survey, conducted as part of the 2007 National Health Interview Survey (NHIS), an annual study in which tens of thousands of Americans are interviewed about their health– and illness–related experiences, visit www.nccam.nih.gov. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Balintfy: Thank you Wally. Stay tuned, part two on proteomics is after this quick break.
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Proteomics—Part 2 of 3—The Challenge of Proteomics for Cancer
Balintfy: In part one of this three part series, on proteomics, the study of proteins, we learned how proteins are the workhorses of DNA, the genetic make–up or blueprints that make us who we are. In this part two, we continue our talk with Dr. Henry Rodriguez, the director of the Clinical Proteomic Technologies for Cancer programs at the NCI. We discuss the challenges of proteomics as a tool for early detection of cancer. First, Dr. Rodriguez, welcome back.
Dr. Rodriguez: Thank you.
Balintfy: What are some of the challenges of studying cancer proteins and expanding the number of cancers that can be identified through testing for protein biomarkers?
Dr. Rodriguez: I think the key message here is what we have is the lack of well–characterized different platforms, either for the discovery or the verification of different protein markers coupled with the lack of various performance standards, metric software, necessary reagents and, of course, biospecimen collection protocols, or standard operating procedures, that ultimately can be used across multiple institutions or laboratories. And this ultimately seems now to limit the number of cancer protein or biomarker tests that eventually become available to the general public.
Balintfy: Metrics is something we use here at the NIH a lot, but maybe the general public doesn’t really know what we mean when we’re talking about metrics or measurement and how that would make a difference in validating the science. Can you touch on that a little bit?
Dr. Rodriguez: Yeah, so what becomes quite important is when one laboratory actually does experiments, if you really want to test a robust list and actually look at what you’re measuring, it becomes very important to have multiple institutions to be able to reproduce that for you. Well, the way that’s typically is going to be done is you need to come across your network and say, "Let’s develop standard ways of doing this so you can have the assurance that what we’re measuring in one laboratory is not going to be attributed to the way that laboratory happens to have done it." To make it very robust, when we have assurance of what we’re looking at and it’s valid from a biological perspective—it’s not going to be attributed to bias—multiple institutions should have that ability to measure that same animal and come up with those same conclusions.
Balintfy: Maybe this is an oversimplification, but I would think of it as, you know, you can have one recipe in one kitchen, and it should turn out the same as the recipe in the other kitchen.
Dr. Rodriguez: Right, so and if you use that in an analogy, technically you have different cooks at each one of these kitchens, but the question becomes just how good is the oven that we’re using? Just how good is that recipe we’re using? Because if you begin to cook and develop the same cake at the end, then that tells you that what you’re developing, all that is going to be very robust.
Balintfy: Great. Are there some problems associated with those making sure that those laboratories and the matrixes are consistent?
Dr. Rodriguez: You know, one way of looking at it is you can kind of look at the challenges that exist when it comes to this field. If you simply look at the scientific literature today, what’s remarkable is now there’s over a thousand. Let me say that again. There’s over 1,000 cancer protein biomarker candidates that have been identified by the research community over the past 10 years at least. And this list continues to grow on a daily basis. Now, the challenge is that very few of these protein biomarker candidates ultimately make their way into a clinical setting. Part of the reason is that today, laboratories across the country and around the world collect, store, and they study proteins in different ways.
Balintfy: So what are some advances you think are necessary to resolve these problems?
Dr. Rodriguez: So current and emerging protein measurement technologies, they really need to be optimized and calibrated through the use of standards, ultimately to produce comparable results between these laboratories that I’ve alluded to. At the same time, high quality reagents are going to be needed.
Balintfy: So what exactly is a reagent?
Dr. Rodriguez: A reagent happens to be a physical material that you use that you will run through your instrument to make sure that it’s working correctly.
Balintfy: So that’s just one of the resolutions that’s needed, and there are others as well in terms of technology?
Dr. Rodriguez: Yeah, exactly. So I think one of the good things about NCI is that through the Clinical Proteomics Technologies for Cancer, it actually developed as a very elaborate network. That network is actually looking at the existing platforms that are today. But the other thing we have to ask the question, are the technologies we have today going to be the ones that are going to be required let’s say five, 10 years from now? So I think you should always be looking at, can we develop better tools, both from a hardware perspective and a software perspective, to mine the vast amounts of data that’s being generated.
But I think one of the main things that I want to emphasize I think that’s going to be very necessary is team science. I think this is something that’s absolutely critical, especially for these sorts of large scale initiatives. When it comes to seeing science, the reality, especially when it comes to proteomics, is that an interdisciplinary team based approach is what’s going to be the most valuable. No one laboratory, that’s the reality, working on its own could possibly examine all the potential biomarkers, develop all of the necessary technologies for isolating and validating the biomarkers for research or clinical use, or assemble all of the pieces of evidence that’s going to be required to understand the molecular mechanisms of cancer.
The bottom line, it’s going to require many laboratories working together ultimately to accomplish those goals.
Balintfy: It’s much like the Human Genome Project.
Dr. Rodriguez: It’s very similar to the Human Genome Project, and in fact, one of the things I want to emphasize is that within that project, one of the things that allowed it to be very successful because it did involve multiple laboratories and it was an international effort, is that they helped standardize the various methodologies and the various platforms and the way the data was going to be analyzed. And proteomics is kind of falling along the same lines. It’s that it’s a huge area. Clearly, individual laboratories are always critical because you’ll always get very good signs, but for large–scale initiatives, pulling the collectiveness together would also contribute very much to move the field forward.
Balintfy: And this is going to be a large–scale effort, isn’t it?
Dr. Rodriguez: Absolutely.
Balintfy: Do you think after these guidelines are set up that there’ll be similar achievements like there was with the Human Genome Project?
Dr. Rodriguez: Yes, so it’s interesting. Right now, the research community is actually debating that question. So the question becomes, "Are we at a stage now where we could tackle such a large–scale effort?" I think the jury is still out, especially attributed to all the complexities that the protein world happens to bring to it versus the DNA world. I do think over time that will be something that could be obtained, but I think at the present time, what we need to do is just give ourselves the assurance that we know how to develop the proper pipelines. Once we could test that and show that we now achieve that goal, then we could start asking ourselves, what would be the next sort of initiative that could capitalize now on what we’ve developed in terms of this pipeline and the very robustness behind the pipeline?
Balintfy: Great. So in our next episode, we’re going to be talking in more specifics about some of the programs that NCI is offering. So I’m looking forward to that one and thanks very much.
Dr. Rodriguez: You’re welcome.
Balintfy: Dr. Henry Rodriguez at NCI. For more information about the NCI Clinical Proteomic Technologies for Cancer Initiative, visit the website proteomics.cancer.gov. And be sure to tune in, in two weeks for the last of our series on proteomics. For now, that’s it for this episode of NIH Research Radio. Please join us again on Friday, April 17 when our next edition will be available for download. I'm your host, Joe Balintfy. Thanks for listening.
NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.