August 13, 2010
NIH Podcast Episode #0115
Host: Welcome to the 115th 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, and coming up in this episode an in-depth discussion on skin cancer, learn about it and how to protect yourself; also, details on how researchers see new ways the brain protects itself from blockages. But first, this news update. Here’s Craig Fritz.
Fritz: The Eunice Kennedy Shriver National Institute of Child Health and Human Development recently released two studies that may have significant implications for women’s health.
In the first study, researchers at NICHD and the University of Oxford found that women who exhibit higher levels of stress may have more difficulty becoming pregnant. The researchers showed that women who had higher levels of a substance called alpha-amylase were less likely to get pregnant than were women with lower levels of the substance. Alpha-amylase is secreted into saliva by the largest of the salivary glands. In recent years many researchers have used it as a barometer of the body's response to physical or psychological stress.
In the second study, NICHD researchers found that women's cholesterol levels correspond with monthly changes in estrogen levels. This natural variation, they suggest, might indicate a need to take into account the phases of a woman's monthly cycle before evaluating her cholesterol measures. On average, the total cholesterol level of the women in the study varied 19 percent over the course of the menstrual cycle. Total cholesterol was found to be the lowest just before menstruation began and increased as women neared ovulation. Further research may help clarify the optimal point in the cycle for doctors to measure women’s cholesterol levels and help clinicians develop standardized procedures for measuring cholesterol in premenopausal women and determining their heart disease risk.
And finally, researchers at the National Institute of Allergy and Infectious Diseases have reported that they have begun human clinical trials for a dengue virus vaccine. Dengue is a tropical and subtropical virus carried by mosquitoes. It infects 50 to 100 million people every year. Several recent cases have been reported in Florida.
For this NIH news update, I’m Craig Fritz.
Balintfy: News updates are compiled from information at www.nih.gov/news. Coming up next everything you need to know about skin cancer. Stay tuned.
(BREAK FOR PUBLIC SERVICE ANNOUNCEMENT)
Insight on Skin Cancer
Balintfy: We’re in the dog days of summer and gearing up for the Labor Day Holiday, making it a good time to get a refresher on skin cancer. In this in-depth interview, we hear from Dr. John DiGiovanna, a dermatologist in the Dermatology Branch at the National Cancer Institute. We jump right in with what is skin cancer?
Dr. DiGiovanna: Skin cancer comprises a couple of related problems. The most common skin cancer is basal cell carcinoma and squamous cell carcinoma, and there are many, many of those in the U.S. every year. Probably the most recent estimate’s more than three million. Melanoma is less common, probably about 120,000 of those in the U.S. each year, and there are a few different types. Melanoma can arise on normal-appearing skin, and when it does that it can either appear as a flat area; usually it has a color to it that’s different from the surrounding skin, or an area that has some sort of a nodularity to it, so you can actually — it’s sort of like a marble, and you can actually feel.
So, the ones that start as flat have a period of time where they grow on the surface of the skin, and those are called superficial spreading melanoma. With those we have a period of time before they grow deep. The ones that start that are nodular, or that are sort of like a marble, those can have — at very early on can have an invasive property or an invasive growth rate. Those can be a little more problematic earlier on. But melanoma can also occur from pre-existing lesions. So, we can — people can have moles on their skin, what we usually call nevi, that can remain static for a long period of time and then develop into melanoma from the moles.
There’s another type of melanoma that develops in sun-exposed areas that occurs from lesions we call lentigos. So, when young children go out into the sun and get a burn, they may develop freckles. But over many decades in sun-exposed areas, many individuals who are light-skinned will develop larger brown or tan areas called lentigos, and melanoma in sun-exposed areas can occur from these lentigos, and that’s called lentigo maligna melanoma.
And finally, there’s another type of melanoma that occurs in acral areas, on the palms and soles, and that’s more common in Asian and darkly skinned individuals, Africans and African Americans, and that’s called acral lentiginous melanoma. So there’s a spectrum of different types of melanomas.
Balintfy: And it sounds like there are different types of people that are at risk for these different types of melanomas. So, who exactly is at risk and how would they get it? It doesn’t sound like it always comes from the sun. These different types of skin cancers can come in different ways.
Dr. DiGiovanna: That’s correct, and that’s why it’s been a little bit complicated to fully understand it when we use the one word “melanoma.” So, there are some individuals who have many moles, and that can be a risk factor for melanomas. And in some rare individuals they inherit a gene abnormality where their moles appear, clinically when you look at them, as irregular, and also irregular under the microscope, or dysplastic, and these individuals are at increased risk of developing melanoma in these moles, and that may run in families.
The acral lentiginous melanoma occurs more commonly in Asian and darkly skinned individuals and on the palm and sole, where really we’re not talking about sun exposure as a major risk factor. But light-skinned, Caucasian individuals who have skin that burns easily and may tan very poorly, those are the individuals who have the greatest amount of increase in risk from sun exposure and sun burning, and those are the ones that need to be particularly careful about sun protection from various mechanisms: using protective clothing, hats, sunscreen.
Balintfy: And that’s exactly what I wanted to get to next, is how can people protect themselves from the risks — risk factors from melanoma? I guess if it’s genetic, there’s nothing you can do.
Dr. DiGiovanna: That’s not quite true. If someone knows their risks, they can manage it much better, so if an individual knows they’re at a genetic risk for melanoma because they carry a particular gene, then it’s important for them to do skin self-evaluations and to have very competent dermatologic evaluations. If an individual’s risk is high because they have a family history of melanoma or a personal history of melanoma, if they’ve had blistering sunburns in the past, they also can derive a great deal of benefit from self-examination, from dermatologic examination, but they can also use measures to protect themselves from excessive ultraviolet radiation.
So, they should not be out in the most intense hours of sunlight during the day, from 10:00 until 2:00 or 3:00, without protection, and protection would mean a broad-brimmed hat, long-sleeved clothing, and in areas that can’t be covered, using sunscreens.
And the issue with sunscreens is often, what sunscreen should I use or how can I interpret an SPF? Well, the SPF is a factor, sun protective factor, and that is used primarily to gauge protection against UVB. So, what is UVB? Well, the ultraviolet spectrum is divided into A, B, and C. Ultraviolet C is germicidal wavelength, and the ozone layer protects us from that, so it doesn’t reach the Earth’s surface. Ultraviolet B is what causes a sunburn if you go out and you have light skin; you’ll burn in a short period of time. Ultraviolet A long is wave light, and that doesn’t penetrate -- that does penetrate through window glass, so you can get a sunburn through window glass, and you get that from UVA, and that’s also the wavelength that is in -- the predominant wavelength in most artificial tanning devices. UVB and UVA have the capacity to cause the damage that causes skin cancer.
So, you’re looking for a sunscreen that protects you against the UV that reaches the Earth, and that’s UVA and UVB, and we measure them -- the measurement they have is the SPF, or sun protective factor. So you should look for a sun protective factor of 15 or higher. You should apply it probably 10-15 minutes before you go outdoors and then reapply it, if you’re going to be out for a long period of time, at least every two hours. You should apply an amount equivalent to, let’s say, an ounce, or a palm-sized area, if you’re trying to cover the areas that would be exposed, let’s say, when you wear shorts, or face, neck, arms, and legs. If you’re wearing less than that, you probably will need more than that, so you may need two palm-sized areas if you’re in a bathing suit.
And you want to recognize that sunscreen is a measure of protection. It doesn’t — it’s not complete protection like a suit of armor, so if you stay out longer time than you would when you would burn without sunscreen, you can actually increase your risk by getting a huge amount of ultraviolet radiation exposure. So, it needs to be used prudently if it’s going to be used helpfully.
Balintfy: Because I understand it also works differently in the time of day that you’re out, that an hour’s worth of — or maybe a better example is 15 minutes of sun exposure in the morning is totally different than 15 minutes of sun exposure at high noon.
Dr. DiGiovanna: Yeah, high-noon sun exposure, and even worse maybe 3:00 sun exposure, is very intense, and a short sun exposure there will cause a lot more damage the same day under the same circumstances than before 10:00. So that’s why we ask people to be particularly concerned between 10:00 and 3:00, because that’s when the sun is going to be most intense. And cloudiness doesn’t protect you from ultraviolet radiation. The risk isn’t visible light, it’s ultraviolet, and ultraviolet will penetrate, so people can get sunburn on a cloudy day; they can get sunburn if they’re in the water, in the pool, and they should be aware of that.
Balintfy: And also in the pool or in the beach, in the ocean, that could wash off the sunscreen.
Dr. DiGiovanna: Yes, it does. There are an excellent spectrum of sunscreens available. So, if someone is going to be doing outdoor sporting activities, there are sunscreens that are made to feel comfortable on the skin for that. If you’re going to be doing water activities, there are sunscreens that are waterproof and that will be very resistant to washing off. And if you’re going to be wearing business clothes and you don’t want to put oil on your skin and then a white shirt and a tie, there are sunscreens that are gels that don’t make the skin oily. But you do -- if you are going to be out and you are going to be doing watersports or running and sweating, you really do need to reapply the sunscreen every two hours to keep it being effective.
Balintfy: Excellent. Before we wrap up, what are some of the latest research — what is the latest research telling us about identifying, preventing, treating melanoma? What’s new there?
Dr. DiGiovanna: For identifying, we like to instruct patients in how to do a self-exam. We used to tell people to follow the A, B, C, Ds of melanoma of pigmented lesions. The A stood for “asymmetry,” so your right ear is shaped very much like your left ear, so a skin lesion that has a shape that’s different from one side to the other raises a little concern. The B stands for “borders” or “irregular borders,” so if it’s nice and round, that’s good. If it’s jagged and rough and different parts are growing differently, then it’s of a little more concern. The C stands for “color,” so many colors is a little bit of concern. And the D for “diameter,” so larger than a pencil eraser. The new thing is they’ve added to that an E for “evolving.” So lesions that people find that they think have changed within the prior few weeks or months, that’s another cause for concern.
For diagnosis, we’re really good at doing skin exams. One of the tools that’s newly evolving that helps is called dermatoscopy, and that’s a light set up with a small lens that we use to put against the skin. Actually here at NCI we have a digital dermatoscope that we can use to get great images of skin lesions. We do that in our patients with inherited skin disorders to follow the lesions over time.
With respect to prevention, the newest thing I’m aware of is there have been some really important studies recently showing that risk of indoor tanning and that the risks from tanning devices are now well accepted. The World Health Organization has declared indoor tanning devices as carcinogenic, and the risk now we know holds true regardless of when individuals start, whether they start at a young age or an adult age. So, we’re learning more about what the problems are, and we have good measures to avoid them, and people are interested in doing that.
Balintfy: Great. I think that wrapped up all my questions. Is there anything that you would like to add or maybe something that I missed or something worth re-emphasizing?
Dr. DiGiovanna: A healthy, active lifestyle is great, and there are many outdoor activities that people can enjoy and should, but they need to do them in ways that can protect them. I know a lot of people today are concerned a little bit about vitamin D levels if they don’t get any UV exposure, and we recognize now that vitamin D is important, and the normal levels may be higher than they were years ago. Vitamin D supplementation is easily available in dietary form, and if people are concerned about that, they should have their levels measured and supplemented.
Balintfy: Thank you Dr. John DiGiovanna at the National Cancer Institute. For more information about skin cancers and melanoma, visit www.cancer.gov. Coming up next, findings that may provide insights into age-related cognitive decline, Alzheimer’s disease and recovery from stroke.
(BREAK FOR PUBLIC SERVICE ANNOUNCEMENT)
In Mouse Study, Researchers Discover New Mechanism for Clearing Blockages from Smallest Blood Vessels
Balintfy: Researchers at Northwestern University Feinberg School of Medicine have identified in mice a previously unknown way by which the smallest blood vessels remove blood clots and other blockages from the brain. Dr. Suzana Petanceska [pet-an-CHESS-ka] at the National Institute of Aging explains that the brain is an extremely high-maintenance organ; 20 percent of the heart’s output of blood flow goes to the brain. And the way the brain actually gets enough nutrients and oxygen to properly function is by an extensive network of blood vessels. Those blood vessels begin with the large arteries at the base of the brain and spreads into a myriad of smaller and smaller blood vessels to end with capillaries – the tiniest blood vessels.
Dr. Pentanceska: So, just to illustrate how extensive this blood vessel network is in the brain, if you extend, stretch the network of capillaries out into a single strand, it would go 400 miles.
Balintfy: And what would happen if some of those capillaries stopped working or if there was a blockage?
Dr. Pentanceska: So, what we have known so far is that since these are very fine blood vessels and they are prone to being obstructed to tiny microclots spontaneously occurring in them and clogging them, so the body has developed a number of mechanisms to actually eliminate spontaneously occurring blood clots in these vessels. One is by what is called hemodynamic forces; clots are being just pushed through or squeezed through. The other mechanism engages the anticoagulant activity of the blood — that exists in the bloodstream, so these clots are degraded.
Balintfy: Because in general, a big blood clot I think the general public understands that that’s a stroke, so when the brain does not get the oxygen delivered by the blood, that’s a bad thing.
Dr. Pentanceska: Right; that’s a bad thing. Obstructed blood flow, even in the tiniest microvessel, has negative consequences on the connections between nerve cells, which is how they communicate and this is how the brain operates, and on the general health of individual nerve cells.
Balintfy: But you said just a second ago that these small blood vessels, they are routinely removing clots.
Dr. Pentanceska: They are — we have known that they routinely — both clots occur in them, but there are mechanisms by which they get rid of them.
Balintfy: Okay. But the scientist reported recently in “Nature” a discovery of a new way that microvessels in the brain can be cleared; can you explain what they found?
Dr. Pentanceska: So, just as we know that there are ways for the microvessels to maintain blood flow, we also know that clots are not always cleared.
So, the scientists were really curious to further investigate mechanisms that microvessels may utilize to eliminate blood clots and to also examine the consequences when blood clots are not removed.
So, this was a study conducted in mice, where they used some cutting-edge new technology that allowed them to visualize — first, introduce glowing microclots into the tiniest blood vessels, and then to visualize when and how they are removed. So, they noticed — and this is something that we had known already — that just a couple of hours after a microclot is lodged into a microvessel, many of them are cleared by what I just described: the hemodynamic forces that squeeze them through or through the anticoagulant properties of the — existing in the bloodstream.
So, a number of clots, though, remained lodged, and so the scientists were curious what are the consequences of this process and then followed the fate of these clogged microvessels. So, what they were really dismayed to find out is that a couple of days later, many of these clogged microvessels were clear again. So, they zoomed in with some really high-powered microscopy to hone into what happened to these microvessels who, only a couple of days ago, were clogged? So, what they found out when they zoomed in on the cells that lined the capillaries is that these — known as endothelial cells basically reach out around, surround the — engulf the clot and push it out of the microvessels. And then they again line up and down the vessel as if nothing happened. And just as blood flow was obstructed to that point, blood vessels now start streaming through.
So, this was fascinating; this was neither anticipated nor previously described. And this process goes on for a number of days, and this was what they viewed as two to seven days after they had introduced these microclots.
Balintfy: The study was in mice, but I’m guessing that there are some potential implications for humans and the diseases we face. What are the researchers looking ahead?
Dr. Pentanceska: Well, absolutely, although these are early stages and this discovery needs to be followed up by much more research both in mice as well as in humans to uncover how conserved this mechanism is in humans first, also to discover to molecular events involved in this process.
So, obviously, the fact that this process was uncovered has a number of implications. First, this may hold true in other organs, not just the brain, and it is important in terms of understanding microvascular resilience in a number of body organs. Second is that given that this process may be compromised and less efficient in the aged brain, this may be part of the mechanism by which age-related cognitive decline occurs in humans, and this may also play into what are the early pathogenic steps for neurodegenerative disorders such as Alzheimer’s disease that has a huge cognitive component. This also may play a role in processes that follow after stroke, processes that are required for recovery after stroke. What happens after stroke, there is reperfusion, or revascularization of the tissue, and a lot probably may rely on the effectiveness of this protective mechanism in terms of the tissue — the brain tissue coming back and recovering from stroke injury.
I think another wonderful consequence of this study is that it really opens a new line of investigation. Certainly, finding out something completely new that can have such relevance to human brain health is a wonderful thing and will keep a lot of scientists busy for a number of years to come. Another consequence is that this, in addition to opening doors to a lot of new basic research, also inform therapeutic efforts for age-related cognitive decline, stroke, and may lead to uncovering a number of new, therapeutic targets for these human conditions.
Balintfy: Thanks to Dr. Suzana Petanceska at the National Institute on Aging. For more information about the study and age-related research, visit www.nia.nih.gov.
And that’s it for this episode of NIH Research Radio. Please join us again on Friday, August 27th when our next edition will be available. I’m you host, Joe Balintfy, thanks for listening.
Announcer: 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.