i on NIH Vodcast
October 23, 2009
“i on NIH” Vodcast Episode #0023
Welcome to “i on NIH”!
Featured in this month's episode are segments about a 2009 H1N1 Influenza update, and a discussion about drug delivery.
From the national institutes of health in Bethesda, Maryland – America’s premiere medical research agency – this is "i on NIH"!
Covering health-research topics important to you and the nation, this public service vodcast is your information source from inside all 27 institutes and centers at NIH.
Half an hour, once a month, we’ll show you the excitement of advances and the important information that comes from medical research. And now, here’s your host, Joe Balintfy.
Host: Welcome to the 23rd edition of I on NIH. Coming up in this episode, we have an in-depth discussion with Dr. Anthony Fauci about the 2009 H1N1 virus. Also, we'll have an interview with an NIGMS-funded scientist about the inside workings of drug delivery. But first, the NIH Research Update with Harrison Wein. What do you have for us this month, Harrison?
Harrison: This week I'm going to talk about three stories related to sleep and circadian rhythm. One is about a gene that regulates sleep length, the other is about sleep and Alzheimer's disease, and the third about eating when you should be sleeping.
Joe: That sounds great, Harrison. But first tell us: what exactly is circadian rhythm?
Harrison: Circadian rhythm is our internal biological clock. It's tied to cycles of light and darkness and, basically, controls our daily cycles of sleep and activity.
Joe: So the first study you said is about a gene that regulates sleep duration or length.
Harrison: We all know that different people seem to need different amounts of sleep. These tendencies run in families, suggesting they have a genetic basis. Genes affecting sleep duration had been identified in some organisms, but until now no similar gene had been found in people. In a new study, NIH-supported scientists sequenced the DNA of suspected genes in different families, looking for genetic links to extremely early wake-up times.
Joe: And what did they find and how is it significant?
They found a mutation in a gene called hDEC2 in a family with two extremely early risers. Family members who carried this mutation slept an average of six and a quarter hours. Noncarriers in the family averaged over eight hours. They all fell asleep around the same time. The difference is that carriers naturally woke up earlier.
The researchers also found that mice given the mutant human gene stayed awake longer, too.
This is significant because, hopefully, it will put us on a path to understanding why some people need to sleep longer than others. And the insights we gain may lead to new therapies for sleep disorders.
Joe: OK, Harrison. Another study you mentioned is about sleep and Alzheimer's disease. Has this study found a link?
Harrison: We've known that people with Alzheimer's and other neurodegenerative diseases often have trouble sleeping. A new study found that disrupted sleep, at least in mice, can lead to the buildup of brain plaques, which are a hallmark of Alzheimer's disease.
These plaques are made mostly of a compound called amyloid-beta, which is produced by nerve cells and released into the surrounding brain fluid. There seem to be many factors that lead to amyloid plaque formation, but we don't really understand the process yet.
NIH-supported researchers used a technique called microdialysis to monitor amyloid-beta levels in living mouse brains. They found that amyloid-beta levels fluctuate each day, rising during active periods and falling while at rest. The longer the mice stayed awake, the greater the increase in amyloid-beta levels in the fluid that surrounds brain cells.
The researchers traced this effect to a hormone called orexin. Orexin causes the mice to stay awake longer and their amyloid-beta levels to rise. They also tested chronic sleep deprivation in mice and found that it promoted plaque formation. A drug that blocks orexin, though, helped prevent the buildup of plaque.
Joe: So was this strictly a mouse study, or do the findings relate to people as well?
Harrison: Well, the researchers measured amyloid-beta levels in the cerebrospinal fluid of 10 healthy men. They found that the amyloid-beta levels fluctuate in humans with the time of day, too.
Now, that doesn't mean that lack of sleep and orexin necessarily play a role in amyloid plaque development in humans. But if this does prove to be true in people, orexin or compounds it interacts with may one day become new drug targets for the treatment of Alzheimer's disease.
Joe: Sounds good, Harrison. And you had one more study eating during sleep hours. What's the story on this?
Harrison: Here it is in a nutshell: mice fed a high-fat diet when they're normally sleeping had an average 48% boost to their body weight, compared to a 20% increase in mice that ate the diet during their normal waking hours. So that implies that not only what we eat but when we eat may influence our weight.
Joe: Sounds like that has major implications for midnight snackers.
Harrison: Of course, keep in mind that this is in mice. Further research is going to be needed to see if this really sheds light on human weight gain. That said, the circadian clock is known to affect many other body functions: temperature, hormone levels, hunger and sleep, all of which can contribute to changes in weight.
Now, let me wrap it all up by saying that researchers may one day find ways to take advantages of all these findings I've been talking about. But here's what you can do right now: Try to get enough sleep. We've reported on the many health effects of a lack of sleep in our publications, if you want to read more about those.
And two, make sure not to snack mindlessly when you're sleepy, like late at night. You can take in a lot of extra calories that way.
Joe: Good advise, Harrison. And where can people go to find out more?
Harrison: Read about these and other NIH research studies in "NIH Research Matters." Go to the NIH home page and click the link on the right-hand side, under "In the News" that says, "eColumn: NIH Research Matters"
Joe: And what's in this month's health newsletter?
Harrison: This month's cover story is about the things that may be tripping up your efforts at weight control. Other recent stories covered how parents can help kids at school. And we also had a story exploring the health effects of coffee. So lots of good stuff in there.
Joe: And where can people find those?
Harrison: That's at news-in-health-dot-nih-dot-gov.
Joe: Thank you Harrison
Harrison: Thank you Joe.
Host: And now for our first feature. Calvin Jackson recently talked to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, to get the details on the H1N1 flu. Here's the interview with Dr. Fauci.
Q: How can a person tell if they have the regular seasonal flu or if they’ve contracted the 2009 H1N1 influenza virus?
Dr. Fauci: Well for a person, him or herself, to be able to determine that would essentially be impossible because you can get everything from very, very mild illness to severe illness with either seasonal flu or the H1N1 new 2009 pandemic flu.
Most of the time it's a mild disease, but there are unusual cases that can be severe. The only way a person can tell is if they get their blood drawn or other laboratory tests, which could specifically distinguish between one and the other.
But that is something that is not done routinely, so if someone wakes up in the morning and feels that they're not well, they get a fever, muscle aches, a cough—things you would get with the flu — it would be very difficult for them to determine whether it's the seasonal flu or the H1N1. However, circumstances that are going on in the community can give you a pretty big hint of what you have. Let me give you an example.
When H1N1 historically has gone into a community, both in the United States in the spring of 2009 as well as what we're seeing in the southern hemisphere in Argentina, Chile, Australia, in South Africa it generally overwhelms and crowds out the seasonal flu.
So if you're in a community in which we know from surveillance that 99 percent of the cases of flu are really H1N1 you can make a reasonable assumption that your illness is due to H1N1.
If there's a mixture of both or if there's still a lot of seasonal flu in the community, you may not be able to distinguish between one and the other.
Q: This year do I get a shot for the 2009 H1N1 flu in addition to the regular flu shot?
Dr. Fauci: Well you certainly should get your seasonal flu shot. That's for sure. When we talk about the vaccination program for the H1N1 we'd like to be sure that the five priority groups of individuals get the H1N1 that becomes available early on. We fully expect that we would have enough so that you can cover not only the priority groups but anyone else who feels they want it and need it.
So the answer is yes, you should get the H1N1. If you're not in one of the five priority groups then you may need to check with your physician or healthcare provider when it would become available to you. Just to be clear, the five priority groups are pregnant women, people who the caretakers parents what have you — of children less than six months old, healthcare workers, young children and young adults from six months to 24 years old, and individuals from 25 to 64 who have underlying medical conditions that would compromise them and put them at a higher risk for complications.
Q: What should a person do if they get flu-like symptoms? One of the major concerns is that hospitals will be inundated with the "worried well." But at what point should you be concerned enough to seek medical attention?
Dr. Fauci: Well if you have the H1N1 flu, or think you have the H1N1 flu, or even seasonal flu - let's say if you think you have influenza. Most of the time this is a relatively mild illness - it makes you uncomfortable. So what we recommend for people - and this has to do fundamentally with whether or not you should receive treatment with an antiviral drug. So if you have a low grade fever, some aches, some sniffles, a bit of a cough and it doesn't go any further than that, you may want to call up your healthcare provider, explain your symptoms and I'm sure he or she will tell you that you start to have difficulty breathing, really uncomfortable, high fevers, really bad myalgias, you should then come in and get a prescription to get treated, because you want to treat people who have serious disease that either requires hospitalization or may be serious enough to even consider hospitalization.
So a phone call or a visit, depending upon on how severe it is. Importantly, if you happen to fall into one of the four categories that are at high risk for complications — and that's pregnant women, that is young children, that is the elderly individuals older than 65 years old, or individuals who have underlying conditions that compromise them — if you fall under one of those four individuals, you shouldn't wait. You should get your physician to get you a prescription to be treated right away.
If you're otherwise healthy, you use your judgment. Is it mild enough — maybe a phone call, you don't necessarily have to go into an emergency room. In fact, we discourage that unless you are feeling really poorly.
Q: Are there some basic things that people can do to reduce the likelihood of transmission?
Dr. Fauci: Well there are things that people can do to reduce the likelihood of their getting infected and to reduce the likelihood of their infecting others. And let's talk about reducing the likelihood of your getting infected. First thing importantly, wash your hands frequently because we know that you can get infected by touching an inanimate object that someone who is infected touched and then touch your nose, or your lips, or your eyes. Try and stay away as much as possible from rubbing your eyes, or your nose, or your mouth because that's a very good way to transmit the virus. The other thing is to avoid, particularly when there is flu in the community, avoid places where there are people who are sick and coughing and it's a crowded place. Now that's difficult to do — you can't isolate yourself from the rest of the world for the whole flu season, but use some good judgment in that. How you could prevent giving it to others is if you're sick — don't go to school, or parents should not send their children to school if they're sick.
If you're sick, don't go to work. If you're coughing or sneezing, cover it with a tissue or sneeze or cough into your elbow. Do those kinds of things as well as washing your own hands, because you may give it to somebody else from what's on your own hand.
Q: NIAID-sponsored clinical trials of the 2009 H1N1 influenza vaccine, which began in early August, already have some preliminary results. What are the early data showing us?
Dr. Fauci: Well the early data are showing us — we did a bunch of trails and the fundamental questions are is this safe, at least in the short term, are there any obvious safety issues?
Secondly, what is the right dosage to use and how many doses should we give? And what is the sequence of giving it vis-a-vis the seasonal flu vaccine and the H1N1 vaccine?
We have some very good news that we got recently, that first of all as we had expected, since this is very much like the seasonal flu vaccine — that there doesn't appear to be any safety red flags or safety issues. The other important issue is that we were able induce a very powerful response in people — in adults and the elderly — with a single dose of what the classical dosage is, which is 15 micrograms, very typical of what you give with seasonal flu vaccine. That dose not only was effective with a single dose, as opposed to two doses, but it also induced a very potent response within 8 to 10 days of getting vaccinated, which means when you go get your flu shot — the H1N1 — you will induce a response that you could predict would be protective really relatively quickly - within two weeks, 8 to 10 days, is what we found.
Q: There are some people who are concerned about a vaccine and possible side effect. But in talking about 2009 H1N1 flu vaccines you’ve time and again made a very good point: that is, while there is a risk, a slight risk, associated with the 2009 H1N1 vaccine, there also is a risk if you do nothing and are not vaccinated. Can you elaborate on this?
Dr. Fauci: Whenever you make any decision about any intervention that you're going to allow yourself to undergo — be it a drug or a vaccine — you've got to balance the risk of what you're going to do with the benefit that you're going to get from it. So if you look at the theoretical, but very, very, very small risk of there being anything that's going to be deleterious with the vaccine, and yet the fact that we are in the middle of a pandemic and we're seeing a lot of people getting infected and we're seeing that some of them are getting seriously ill — particularly people in these high risk categories, like pregnant women and children and people with underlying conditions — so that the risk of not being protected against influenza balanced against the risk of the vaccine and then the benefit of getting vaccinated versus the benefit of being protected from the influenza that you can get infected — it is no doubt that the balance of risk/benefit strongly favors the benefit of vaccine because of the risk of influenza versus the relatively small risk of the vaccine.
Host: This next segment is a new feature for our vodcast. It's a Findings Videocast from the National Institute of General Medical Science. This interview features an NIGMS-funded researcher who discusses the development of a way to deliver drugs right to the part of the body where they're needed. Machalek: I’m Alisa Machalek, a science writer at the National Institute of General Medical Sciences. I’m here with Dr. Omalola Eniola-Adefeso, a professor of Chemical Engineering, at the University of Michigan. Dr. Eniola, you are developing a way to deliver drugs right to the part of the body where they’re needed to fight infection or disease. Can you tell us why this is important?
Dr. Eniola: The way we do it right now leads to two problems. The first one is we have to use a lot of drugs because we have to feed the entire body before it can get to the right location. The second problem is the fact that every cell in the body does get that drug, so healthy cells are also getting drugs they don’t need, which is what causes a lot of the side effects that we see with many drugs. So being able to put the drug in the right amount, in the right location helps us use only the amount we need so we save money and then we don’t get healthy cells sick.
Machalek: You have decided to approach this issue by putting medicines inside hollow biodegradable plastic beads that closely resemble one of the body’s own ways of fighting disease, namely white blood cells. Can you tell us why white blood cells are a good example of how to deliver drugs to a specific location in the body?
Dr. Eniola: White blood cells are essentially the military of the body. Their job is to keep the human body healthy. And for the most part the neutrophils, which are the coast guard, of white blood cells patrol the body looking for things out of place.
When they get signals from the body at a specific location, which is usually a distress call, the white blood cells can immediately respond, go locally to the site of the problem, and fix the problem.
If you can understand how white blood cells do their job, then we can, we believe we can make plastic beads that can do the same.
Machalek: In trying to design beads with the same capabilities as white blood cells, what have you learned so far?
Dr. Eniola: Well we found that the best performing plastic system that we can design are the ones that matches the white blood cells in their size and shape. The key is that we need the drug to come out once it gets to where we send the plastic beads. We figured that we needed to use biodegradable plastics that can fall apart within days and weeks to release the drugs. The hope is that one day we will see some of these plastic beads that we are designing actually being used to cure human disease.
Machalek: You are studying how white blood cells exit the flow of traffic in the bloodstream, stick to the vessel wall, and move through into the tissue in order to fix diseased or injured tissue. Can you tell us how your background as an engineer gives you special insight into this problem?
Dr. Eniola: As chemical engineers what we learn is how blood or how a fluid flows through a pipe. And we view the human blood vessel as a pipe. And we view the blood flow as a fluid just like water flowing through a pipe. And we have a unique understanding of the forces that come into play when we have a fluid flowing. So with that understanding we are able to predict when and how and if white blood cells can actually find their way through the wall, and what types of pressure they are under once they are on the wall, and how does that translate to their movement into the tissue.
Machalek: What do you think is the most exciting part of your job?
Dr. Eniola: My job lets me be a detective, I come in everyday trying to solve a mystery and the greatest mystery of all that we have in this world is the human body.
Host: And that's it for another episode on I on NIH. If you'd like to see or forward individual segments from this program, they're available on YouTube. Check out the NIHOD channel. Thanks for tuning in and please watch again next time. For I on NIH, I'm Joe Balintfy.
Narrator: "I on NIH" is a public service vodcast from the Department of Health and Human Servives. Produced by NIH News Media Branch, of the Office of the Director, Office of Communications and Public Liaison. Thanks for tuning in. We’ll be back again next month with another episode of "I on NIH."
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