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Nitric Oxide May Protect the Blood-Brain Barrier During Parasite Invasions

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CDC/Blaine Mathison // Public Domain

Illnesses brought on by invasive parasites are especially dangerous because of their ability to cross the nearly impenetrable blood-brain barrier (BBB). Resulting invasion can cause life-threatening inflammation of the brain and the central nervous system. Researchers at the Karolinksa Institute in Stockholm, Sweden studying African trypanosomiasis, or “sleeping sickness”—so named because the illness causes disruption of sleep patterns, among other, more dangerous symptoms—have discovered that nitric oxide (NO) can help maintain the integrity of the BBB, potentially reducing neurological damage. Their results were published in PLOS Pathogens.

Sleeping sickness is considered a “neglected disease,” Martin Rottenberg, professor of infection and immunity at Karolinksa Institute, tells mental_floss. That's the case even though we have made steady progress against it in recent years; in 2014, it affected just 3796 people in 36 sub-Saharan African countries—the first time the number of annual infections dropped below 10,000 in 80 years.

Sleeping sickness is transmitted to humans by the bite of an infected tsetse fly. “The parasite disseminates and replicates in the blood, and somehow it penetrates the brain," Rottenberg describes. "The brain is a protected organ, with a very tight barrier, so we wanted to understand how the barrier was opening and closing.”

They hypothesized that NO, which is produced in response to inflammation and infection in the body, might have a protective effect on the blood-brain barrier. They decided to test this theory using mice they had infected with sleeping sickness. What they found was a mixed bag: on the one hand, the parasite generates an immune response that increases permeability of the blood vessels of the BBB and makes an animal more susceptible to infection. “This immune response is meant to control the parasite, but it also helps it into the brain,” Rottenberg says. On the other hand, it produces nitric oxide, “which puts a brake on the parasites so the infection and disease have a much slower pace in the presence of NO."

Then they created mutant mice that lack the enzyme iNOS, the precursor to NO, and infected them with sleeping sickness. They found that these mice had greater numbers of parasites and host immune cells in their brains. This confirmed their theory that nitric oxide is necessary to fight these infections. Further study revealed that an inflammatory cytokine called tumor necrosis factor (TNF) may be responsible for inhibiting the production of NO.

Further research could attempt to reduce neural inflammation by administering nitric oxide somehow, though that is going to take some time to perfect. According to Rottenberg, “It’s a complicated molecule because it reacts very fast with other molecules, it’s very unstable, and in the case of inflammation that has been linked to damage." 

In the meantime, the researchers found that an antibiotic called minocycline can restore the BBB in mice that lack the iNOS enzyme, and reduce inflammation and parasite numbers in the brain. “I think this can help to treat the sickness a little sooner,” Rottenberg says. 

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Medicine
Why Haven't We Cured Cancer Yet?
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Walkathons, fundraisers, and ribbon-shaped bumper stickers raise research dollars and boost spirits, but cancer—the dreaded disease that affects more than 14 million people and their families at any given time—still remains bereft of a cure.

Why? For starters, cancer isn't just one disease—it's more than 100 of them, with different causes. This makes it impossible to treat each one using a one-size-fits-all method. Secondly, scientists use lab-grown cell lines cultivated from human tumors to develop cancer therapies. Living masses are far more complex, so potential treatments that show promise in lab experiments often don't work on cancer patients. As for the tumors themselves, they're prone to tiny genetic mutations, so just one growth might contain multiple types of cancer cells, and even unique sub-clones of tumors. These distinct entities might not respond the same way, or at all, to the same drug.

These are just a few of the challenges that cancer researchers face—but the good news is that they're working to beat all of them, as this TED-Ed video explains below.

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Health
Skipping Breakfast Could Be Bad for Your Heart
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There are mountains of evidence supporting the claim that breakfast really is the most important meal of the day. Getting something in your stomach in the first hours of the morning can regulate your glucose levels, improve your cognition, and keep your hunger in check. Now new research published in the Journal of the American College of Cardiology points to another reason not to wait until lunchtime to break last night’s fast. As TIME reports, people who skip breakfast are at an increased risk for atherosclerosis, a disease caused by plaque buildup in the arteries.

Researchers surveyed over 4000 men and women between the ages of 40 and 54 living in Spain. After looking at the dietary habits of each participant, they broke them into three groups: people who consumed more than 20 percent of their daily calories in the morning; those who got 5 to 20 percent; and those who ate less than 5 percent.

The subjects who ate very little in the a.m. hours or skipped breakfast all together were 2.5 more likely to have generalized atherosclerosis. This meant that plaque was starting to collect on the walls of their arteries, hardening and narrowing them and increasing the risk for heart attack or stroke. People who fell into the 5 to 20 percent calorie category were also more likely to show early signs of the disease, while those who ate the most calories in the morning were the healthiest.

These results aren’t entirely surprising. Previous studies have shown a connection between skipping breakfast and health problems like high blood pressure, high cholesterol, diabetes, and unwanted weight gain. A possible explanation for this trend could be that waiting several hours after waking up to eat your first meal of the day could trigger hormonal imbalances. The time between getting into and out of bed is the longest most of us go without eating, and our bodies expect us to consume some calories to help kickstart our energy for the day (drinking straight coffee doesn’t cut it). Another theory is that people who don’t eat in the morning are so hungry by the time lunch rolls around that they overcompensate for those missing calories, which is why skipping breakfast doesn’t make sense as a diet strategy.

But of course there are many breakfast skippers who aren’t motivated by health reasons either way: They just don’t think they have the time or energy to feed themselves in the morning before walking out the door. If this describes you, here are some simple, protein-packed meals you can prepare the night before.

[h/t TIME]

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