August 24, 2012
NIH Podcast Episode #0166
Balintfy: Welcome to episode 166 of NIH Research Radio. NIH Research Radio bringing you news and information about the ongoing medical research at the National Institutes of Health – NIH…Turning Discovery Into Health®. I’m your host Joe Balintfy, and coming up in this episode finding a way to make vaccines and antibiotics more stable, and understanding pain, and ways to treat it.“Many people feel that, you know, no pain no gain and they feel almost that it’s morally wrong to treat their pain but that’s not true. It’s really important to try to treat their pain and to relieve it as well as we can”
But first, this news update. Here’s Craig Fritz.
Fritz: NIH-funded scientists are creating 3-D chips with living cells and tissues that accurately model the structure and function of human organs such as the lungs, liver and heart. Once developed, these tissue chips will be tested with compounds known to be safe or toxic in humans to advance research to help predict the safety of potential drugs in a faster, more cost-effective way. Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip. Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs. Scientists say serious adverse effects and toxicity are major obstacles in the drug development process. They hope to accelerate the process of identifying compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients. More than 30 percent of promising medications have failed in human clinical trials because they are determined to be toxic despite promising pre-clinical studies.
Scientists at NIH have identified several factors in people infected with hepatitis c that may predict whether the unusually rapid progression of disease from initial infection to severe liver conditions, such as cirrhosis, will occur. Knowing whether a patient's condition is likely to deteriorate quickly could help physicians decide on the best course of treatment. Symptoms of acute infection with the hepatitis c virus, one of five viruses that cause acute and chronic hepatitis, include fatigue, jaundice and loss of appetite. Between 70 and 80 percent of people infected with the hepatitis c virus develop chronic infection, which over a patient's lifetime may result in severe liver diseases, such as liver cancer and cirrhosis. The disease affects approximately 2.7 million to 3.9 million Americans, according to the CDC. Researchers note that treatment for hepatitis c is often expensive and poorly tolerated. Tools that would enable physicians to better predict the course of disease progression in hepatitis c patients would help guide treatment decisions. This small study is an important step in developing such tools.
For this NIH news update – I’m Craig Fritz
Balintfy: News updates are compiled from information at www.nih.gov/news. Coming up an in-depth conversation about pain research and treatment options, and understanding the “cold chain” – that’s next on NIH Research Radio.
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Vaccine and antibiotics stabilized so refrigeration is not needed
Balintfy: Delivering vaccines and antibiotics to third world countries is a daunting task. Treacherous roads, scarce electricity, and unpredictable weather can all easily thwart a shipment. A key challenge in transporting and storing these potentially life-saving medications is that they must be kept refrigerated, and within tight range: between 35 to 46 degrees Fahrenheit. Too hot or too cold and the drugs quickly lose their potency or effectiveness. Margot Kern shares details on how silk may help reduce or eliminate the need for keeping drugs cold.
Kern: Maintaining the “cold chain” which is the term used to describe the continuous refrigeration of drugs from the time they are manufactured to the moment they are delivered, is one of the biggest challenges in transporting drugs to third world countries. It’s estimated that nearly half of the world’s vaccines are lost every year due to failures in the cold chain. But scientists at Tufts University School of Engineering have recently developed a technology that could eliminate the need for refrigeration. A team lead by Dr. David Kaplan is using silk to protect vaccines and antibiotics from breaking down at high temperatures. I recently spoke with Dr. Rosemarie Hunziker, a program director at NIH’s National Institute of Biomedical Imaging and Bioengineering. Her department funds Dr. Kaplan’s work. She helped understand how silk can work as a stabilizer and what the implications are for this technology. Dr. Hunzkiker, why do drugs such as vaccines and antibiotics need to be refrigerated in the first place?Hunziker: So if you think about when you go to the grocery store, when you come back from the grocery store there are certain things you want to rush into the refrigerator right away and its things like meat and milk and eggs. Those are all things that have lots and lots of protein in them. And that’s why you have to refrigerate them because if there are any stray bacteria around, they will eat at them right away
The antibiotics and vaccines are two examples of things that are very very high in protein content and so they have to be refrigerated pretty much from the time they’re made until just about before they’re used.
Kern: So why silk? It’s not really a new material, it’s been around for thousands of years. What inspired Dr. Kaplan to look at silk in a new light?
Hunziker: It’s not as if Dr. Kaplan woke up one day and said ah, silk, this would be perfect to stabilize these proteins. What happened was that Dr. Kaplan and his team had been working with silk as a biomaterial for decades because he did wake up one day and realize it was a very special material. Anybody that’s watched a spider spin its web or watched a silkworm build its cocoon could tell you that. The material is very strong. It looks like it must be pretty simple to make because it just gets spit out of a part of the animal’s body, so there are a lot of reasons why it would be worth investigating.
Kern: Dr. Hunziker went on to explain that it’s the structure of fibroin—the basic protein found in silk—that gives it its protective capability. Fibroin is folded into many layers called beta sheets. These sheets resemble stacks of paper. And in this formation, many molecules of fibroin can be packed tightly together. So tightly, in fact, that not even water can make its way in.
Hunziker: And this is one of the things that they think is what’s happening in this particular formation is that a protein could find its way and nestle into that protected place and it would be stabilized that way because it would be protected from water and from all the things that water brings you because it’s reactive.
Kern: To test their new silk stabilizers, Kaplan and his team stored the MMR—measles, mumps, and rubella vaccine—for six months at 39.2 degrees Fahrenheit, as well as at 77, 98.6, and 113 degrees. What they found was that the silk maintained the drugs potency, even at the highest temperatures. They also found that antibiotics such as tetracycline maintained nearly optimal activity at temperatures as high as 140 degrees. Dr. Hunziker, what’s the next step in the development of these stabilizers?
Hunziker: Basically, they’ve tested it on enough products to know that it’s not just a to know that it might just be a one size fits all. But they haven’t done it with other proteins yet, but they will.
Kern: And in your opinion, how long do you think it will take for this technology to make it to market?
Hunziker: Very, very hard to predict that. It depends on who’s interested, and what the resources are, and what they can bring to bear and what surprises there are along the way, and there always are, but the nice thing about this that part of the innovation, the core science that is needed has been done by this team. And so I think that this development, my personal opinion, is that it will be faster rather than slower, so I don’t think five years is such a terrible time, but you always have to bear in mind that scientists are always tremendously optimistic. We always think things are going to take less time than they actually do.
Kern: Can you comment on how this technology could change global distribution of vaccines and antibiotics?
Hunziker: So when you think about shipping things that have to be refrigerated. Just think about getting on an airplane. The special handling that’s required on an airplane so that you keep things at the right temperature, a steady temperature and a cold temperature. Now imagine how these things are sometimes shipped by boat, by camel in some cases. We’re talking about the third world here, you can’t put a little refrigerated package on the back of a camel and expect it’s going to be stable for the time that it might take to get this product to where it needs to go.
If you could store it at any temperature, room temperature or even hotter, then it doesn’t matter. That product can get where it needs to go and you know that it will be potent enough to work.
Kern: Kaplan’s team is currently working to develop a single-dose packaging system containing the silk stabilizer and vaccine that would expedite administration.
If you want to learn more about these special silk stabilizers, you can visit to www.nibib.nih.gov. For NIH Radio, I’m Margot Kern.
Balintfy: Coming up, chronic pain and alternative ways to combat it. That’s next on NIH Research Radio.
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Researching pain and treatment approaches
Balintfy: About a month ago, in episode 162 of NIH Research Radio, Margot Kern reported about opioid receptors. In her story, Dr. Jean Chin explained that most of us would recognize how opioid receptors affect people.
Chin: The runner's high that you hear about. When people exercise they feel really good afterwards and that's because of the release of endorphins, and endorphins actually bind to these opioid receptors.
Balintfy: Opioid receptors are also involved in pain: when endorphins are released, or if a medication like morphine or codeine is taken, a similar binding process happens and pain can be relieved. The difference, and problem is that people can get addicted to drugs like morphine and codeine. So I’m talking more about opioid receptors, but specifically regarding pain. I’m joined by Dr. Josephine Briggs, the director of the National Center for Complementary and Alternative Medicine at the NIH and Dr. Catherine Bushnell, the scientific director at NCCAM. Starting with Dr. Bushnell, it seems pain is kind of a complicated thing because in a way, it’s subjective but is there a lot of science behind what we know about pain, isn’t there?
Bushnell: Well there is a lot of science. It is a subjective experience. There is at this point no clear objective measure for me to say you have pain or not. If you go to a doctor and you say you’re in pain, your verbal report is really the best measure we have. Now we, in our lab and other laboratories, we use human brain imaging to actually look at what’s happening in the brain when a person experiences pain and in a sense this can give us some objective measure, but it only can be validated by looking back at what the person’s perception is.
Briggs: That’s one of the reasons I’m so excited to have recruited Dr. Bushnell to come to the NIH is that we have here on the NIH campus really wonderful methods and tools to image the human brain. We have superb resources for studying the modern neuroscience of brain function, and so having her come to join us and bring her long history of leadership in pain research together with the resources here on this campus is really exciting for us.Bushnell: Yes. It’s not only the fantastic physical resources, which they really are, but also the intellectual resources here are amazing for us to be able to establish this research program. Because through the various neurology, mental health, National Institute of Drug Abuse, all of these institutes have scientists that have very complementary expertise and interests.
Balintfy: And researchers are looking at both the physiological pain – looking to see physical changes in the brain – as well as non-pharmacological efforts, those ways that pain can be lessened without drugs. Is that right Dr. Bushnell?
Bushnell: That’s correct. We’re interested in both how pharmacological modulation how various pills that people take for pain, but also the non-pharmacological approaches that people use. People use yoga, they use meditation, they use exercise. There are many modalities that people are using to try to help control their pain and we’re trying to understand the mechanisms as well as the efficacy of these various techniques, and also how these complementary techniques can interact with pharmacological techniques. Because in fact when you use these non-pharmacological approaches, you actually can release chemicals in the brain that are very similar to chemicals that are involved in pharmacological treatments.
Briggs: That’s one of the things I’ve learned from Dr. Bushnell is that there’s really a scientific basis for the notion that relaxation techniques, meditation, yoga may actually change your brain processing of pain in very much the same way that opioids do. So that’s a pretty exciting way to complement the drugs. We all know that the pain medications have really troublesome side effects so being able to use the body’s own mechanisms to help with pain is very exciting.
Balintfy: What are some of those side effects of opiates, like morphine or codeine. Dr. Bushnell?
Bushnell: So when you take an opiate, you have opiate receptors all over your brain and other parts of your body. So some of the side effects like constipation are related to opiate receptors in the gut and many of the side effects like respiratory depression or some of the cognitive effects those are avoided if you use psychological techniques that release only specific opiates. I mean opiates into very specific receptors. So it’s kind of a nice way of being able to avoid some of the side effects, but get the therapeutic effect for pain.
Balintfy: And pain is something that not only is subjective, but it’s affecting people in a lot of different ways. For example chronic pain. Do you have some statistics in terms of how many people are affected? Dr. Birggs?
Briggs: The Institute of Medicine just completed a very thorough assessment of pain and pain research in the country. The numbers cited by the Institute of Medicine are that more than a hundred million people in the US are estimated to live with chronic pain. So the impact is really huge. The commonest complaint is chronic back pain and the portion of Americans who in their lifetime will have chronic back pain is huge. In fact, most people have chronic back pain at some point in their life. So learning more about management strategies that will help with this problem is really critical for the country.
Bushnell: And research is showing us that chronic pain goes beyond the pain itself. That when people have pain for many years, in fact it has detrimental effects on their brain. It can lead to some cognitive impairment that people can’t remember things as well as they did before and we find that when we look at the brain in fact it’s kind of like a premature aging of the brain that we see with somebody who has chronic pain.Balintfy: Those sound like troubling findings and I’m sure there’s lots of misconceptions about pain as well. For example, I may think that the pain is in my back, but it’s actually in my head.
Bushnell: You’re right. All pain is ultimately in your head and it’s interesting because some pain it’s very obvious where it’s coming from if you’ve smashed your foot in an accident and everybody feels sorry for you then because they see this horrible injury and you have pain. But many people have pain that you can’t see the injury and it has a problem socially that people they’re not believed and then they start doubting themselves even. More and more the chronic pain disorders that we’re finding with our aging population, neuropathic pain related to diabetes or even after cancer treatments people can have nerve damage that leads to chronic pain that you can’t see the origin of. So it’s a social problem as well as a medical problem.
Balintfy: Are there resources available for people look into regarding pain management? Dr. Briggs
Briggs: Well we have on our website a variety of resources available to the public to help them understand some of the strategies for non-pharmacologic management of pain. The National Institute of Drug Abuse also has a lot of resources. So the NIH does a lot of work to develop strong resources for the public. One of the things that we’re proud of right now is a video that we recently developed, which shows several of or investigators who are studying yoga and one of them is an investigator George Salem who studies the mechanics, how yoga postures affect the body. And is an investigator Karen Sherman who is an investigator in Washington State and she’s done some studies on yoga for chronic back pain. But in this video, we explained to people that they really should when they’re looking for help with this kind of condition first of all talk to their primary care doc, but also really listen to their bodies when they’re doing yoga and also look for an instructor who will be attentive to their personal needs. Many yoga instructors have become quite expert at helping people find the right postures for them and we find that in a number of healthcare settings people are incorporating, offering yoga classes by instructors who are experienced at working with people with pain conditions. But making sure that the approach is gentle and appropriate to you is very important.
Bushnell: I guess another technique that NIH has investigated is tai chi as a more gentle form of exercise that frequently can be used with chronic pain patients and older patients.
Briggs: Now I want to interject one interesting thing about Dr. Bushnell. Dr. Bushnell is also a rock climber and so --
Briggs: And she describes when she talks about pain the experience of clamoring up this cliff and stubbing your toe and how when you’re up there in this terrifying situation you don’t notice the pain of stubbing your toe. It’s of course one of the interesting things about pain is that you can get distracted from pain by the circumstances you’re in. But Dr. Bushnell can talk about that --
Bushnell: Well we’ve been looking at the brain mechanisms and something so simple as distraction we find there are powerful mechanisms in the brain that lead to pain reduction that can be comparable to giving somebody a clinical dose of morphine and just by learning to distract one’s self from pain. So I think these are things that can be incorporated into people’s everyday life and I think it’s something that healthcare professionals need to be aware of. Because certain things like giving a patient a pain diary to fill out, well it’s useful to get that information to understand the nature of somebody’s pain, but if you have them thinking about their pain every hour of every day, then in fact you’re teaching them to focus on the pain. So I think it’s important for healthcare professionals and the general populace just to be aware of these simple factors can have such a profound effect.
Balintfy: Thanks to both Dr. Catherine Bushnell and Dr. Josephine Briggs, from the National Center for Complementary and Alternative Medicine here at the NIH. For more information about pain research and alternative medicine, visit www.nccam.nih.gov.
Balintfy: That’s it for this episode of NIH Research Radio. Please join us again on Friday, September 7 when our next edition will be available. If you have any questions or comments about this program, or have story suggestions for a future episode, please let me know. Send an email to NIHRadio@mail.nih.gov. Also, please consider following NIH Radio via Twitter @NIHRadio, or on Facebook. Until next time, I'm your host, Joe Balintfy. Thanks for listening.
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