Fermentation byproduct suppresses seizures in nerve agent poisoning

A compound found in trace amounts in alcoholic beverages is more effective at combating seizures in rats exposed to an organophosphate nerve agent than the current recommended treatment, according to new research published Read more

Post-anesthetic inertia in IH

A recent paper from neurologists Lynn Marie Trotti and Donald Bliwise, with anesthesiologist Paul Garcia, substantiates a phenomenon discussed anecdotally in the idiopathic hypersomnia (IH) community. Let’s call it “post-anesthetic inertia.” People with IH say that undergoing general anesthesia made their sleepiness or disrupted sleep-wake cycles worse, sometimes for days or weeks. This finding is intriguing because it points toward a trigger mechanism for IH. And it pushes anesthesiologists to take IH diagnoses into Read more

How much does idiopathic hypersomnia overlap with ME/CFS?

If hypersomnia and narcolepsy are represented by apples and oranges, how does ME/CFS fit Read more

exercise

When circulating ambulances disappear

Someone driving around a city on a regular basis will see ambulances. At times they’re going somewhere fast; sometimes they’re just driving. What if, on a given day, fewer ambulances are visible?

One possible conclusion might be: the ambulances are away responding to a group of people who need help. This effect resembles what Arshed Quyyumi and colleagues from Emory Clinical Cardiovascular Research Institute observed in a recent paper, published in the Journal of the American Heart Association.

Arshed Quyyumi, MD

Quyyumi’s team looked at progenitor cells, which circulate in the blood and are attracted to sites of injury.  In a group of 356 patients with stable coronary artery disease, the researchers saw that some (31 percent) had “ExMI” – exercise-mediated myocardial ischemia. That means impairments in blood flow were visible via cardiac imaging under the stress of exercise. This is a relatively mild impairment; participants did not report chest pain. This paper emerges from the MIPS (Mental Stress Ischemia Prognosis) study, 2011-2014.

The ambulance-progenitor cell analogy isn’t perfect; exercise, generally a good thing, increases progenitor cell levels in the blood, says co-first author and cardiology fellow Muhammad Hammadah. The study supports the idea that patients with coronary artery disease may benefit from cardiac rehab programs, which drive the progenitor cells into the ischemic tissue, so they can contribute into vascular repair and regeneration. Read more

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Anti-aging tricks from dietary supplement seen in mice

Our recent news item on a Cell Reports paper from ShiQin Xiong and Wayne Alexander describes a connection between two important biological molecules: the exercise-induced transcription coactivator PGC1-alpha and the enzyme telomerase, sometimes described as a “fountain of youth” because telomeres protect the ends of chromosomes.

While the Emory researchers did not directly assess the effects of exercise in their experiments, their findings provide molecular clues to how exercise might slow the effects of aging or chronic disease in some cell types.

Xiong and Alexander found that the dietary supplement alpha lipoic acid (ALA) can stimulate telomerase, with positive effects in a mouse model of atherosclerosis. ALA is a sulfur-containing fatty acid used to treat diabetic neuropathy in Germany, and has previously been shown to combat atherosclerosis in animal models. The Emory authors’ main focus was on vascular smooth muscle cells and note that more study of ALA’s effects on other cell types is needed.

Below are four key references that may help you put the Cell Reports paper in context: Read more

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Are TrkB agonists ready for translation into the clinic?

Our recent news item on Emory pathologist Keqiang Ye’s obesity-related research (Molecule from trees helps female mice only resist weight gain) understates how many disease models the proto-drug he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in. We do mention that Ye’s partners in Australia and Shanghai are applying to begin phase I clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.

Ye’s 2010 PNAS paper covered models of Parkinson’s, stroke and seizure. Later publications take on animal models of depression, Alzheimer’s, fear learning, hearing loss and peripheral nerve injury. Although those findings begin to sound too good to be true, outside laboratories have been confirming the results (not 100 percent positive, but nothing’s perfect).  Plenty of drugs don’t make it from animal models into the clinic, but this is a solid body of work so far.

 

 

 

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Extend that New Year’s energy – to what benefit?

Surveys indicate that many of us make New Year’s resolutions to eat more healthily or exercise more frequently, yet do not sustain the enthusiasm of January throughout the year.

What if the burst of energy and good intentions could be maintained over a longer period, perhaps with the help of a coach? What kinds of health benefits would appear?

Researchers from Emory and Georgia Tech recently published an analysis of the changes in the health profiles in 382 Center for Health Discovery & Well Being participants who completed a one-year evaluation.

The senior author is Greg Gibson, PhD, professor of biology and director of the Center for Integrative Genomics at Georgia Tech. Georgia Tech postdoctoral fellow Rubina Tabassum, now at the University of Helsinki, is the first author.

“What do most people in developed countries need to do? Eat better, exercise more regularly and stress less,” Gibson says. “It’s unclear whether most of the impact comes from the interaction with partners, or simply from participation and goal-setting, but the overall effect is quite good.”

The main points:

*These are “essentially healthy” people — healthier than the general population in the United States – but almost half started out with high blood pressure and cholesterol levels. There was no control group, and not everyone pursued the same exact program. The average age was 48 years and 28 percent of the group was considered obese. That’s less than the United States population as a whole.

*On average, the 382 participants lost a moderate amount of weight (it works out to about three pounds) and saw their blood pressure and LDL-cholesterol go down significantly over that first year (121 to 116 mmHG for systolic BP, 112 to 105 mg/dL for LDL-C). They also reported lower scores for depression and anxiety.

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Epigenetic changes in atherosclerosis

If someone living in America and eating a typical diet and leading a sedentary lifestyle lets a few years go by, we can expect plaques of cholesterol and inflammatory cells to build up in his or her arteries. We’re not talking “Super-size Me” here, we’re just talking average American. But then let’s say that same person decides: “OK, I’m going to shape up. I’m going to eat healthier and exercise more.”

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Let’s leave aside whether low-carb or low-fat is best, and let’s say that person succeeds in sticking to his or her declared goals. How “locked in” are the changes in the blood vessels when someone has healthy or unhealthy blood flow patterns?

Biomedical engineer Hanjoong Jo and his colleagues published a paper in Journal of Clinical Investigation that touches on this issue. They have an animal model where disturbed blood flow triggers the accumulation of atherosclerosis. They show that the gene expression changes in endothelial cells, which line blood vessels, have an epigenetic component. Specifically, the durable DNA modification known as methylation is involved, and blocking DNA methylation with a drug used for treating some forms of cancer can prevent atherosclerosis in their model. This suggests that blood vessels retain an epigenetic imprint reflecting the blood flow patterns they see.

Although treating atherosclerosis with the drug decitabine is not a viable option clinically, Jo’s team was able to find several genes that are silenced by disturbed blood flow and that need DNA methylation to stay shut off. A handful of those genes have a common mechanism of regulation and may be good therapeutic targets for drug discovery.

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Signs of future high blood pressure in college football players

College football players tend to have stiffer arteries than other college students, even before their college athletic careers have started, cardiology researchers have found.

Although football players had lower blood pressure in the pre-season than a control group of undergraduates, stiffer arteries could potentially predict players’ future high blood pressure, a risk factor for stroke and heart disease later in life.

Researchers studied 50 freshman American-style football players from two Division I programs, Georgia Tech and Harvard, in the pre-season and compared them with 50 healthy Emory undergraduates, who were selected to roughly match their counterparts in age and race. The research is part of a longer ongoing study of cardiovascular health in Georgia Tech college football players.

The results were presented Saturday at the American College of Cardiology meeting in Washington DC, by cardiology research fellow Jonathan Kim, MD. Kim worked with Arshed Quyyumi, MD, director of Emory’s Clinical Cardiovascular Research Institute, Aaron Baggish, MD, associate director of the Cardiovascular Performance Program at Massachusetts General Hospital, and their colleagues.

“It’s remarkable that these vascular differences are apparent in the pre-season, when the players are essentially coming out of high school,” says Kim. “We aim to gain additional insight by following their progress during the season.”

Despite being physically active and capable, more than half of college football players were previously found to develop hypertension by the end of their first season. Professional football players also tend to have higher blood pressure, even though other risk factors such as cholesterol and blood sugar look good, studies have found. Researchers have previously proposed that the intense stop-and-start nature of football as well as the physical demands of competitive participation, such as rapid weight gain, could play roles in making football distinctive in its effects on cardiovascular health.

In the current study, the control undergraduates had higher systolic and diastolic blood pressure than the football players: (football players: 111/63; control: 118/72). However, the football players displayed significantly higher pulse wave velocity, a measure of arterial stiffness (football: 6.5 vs control: 5.7). Pulse wave velocity is measured by noninvasive devices that track the speed of blood flow by calculating differences between arteries in the neck and the leg.

“It is known that in other populations, increased pulse wave velocity precedes the development of hypertension,” Kim says. “We plan to test this relationship for football players.”

The football players were markedly taller and larger than the control group (187 vs 178 centimeters in height, body mass index 29.2 vs 23.7). The football players also reported participating in more hours of weight-training per week than the control group (5.4 vs 2.6).

 

 

 

 

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Nitrite: from cured meat to protected heart

Nitrite may be best known as a food additive used in cured meats such as hot dogs, but medical researchers are studying how it could treat several conditions, including preventing damage to the heart after a heart attack.

Leaders in the nitrite field are meeting May 11 -13, 2011 at Emory Conference Center in Atlanta. One of the lead organizers is David Lefer, PhD, professor of surgery at Emory University School of Medicine and director of the Cardiothoracic Research Laboratory. Lefer discusses the beneficial effects of nitrite in the video below. More information about the meeting is available here.

Scientists think supplying a pulse of nitrite can reduce injury to heart tissue coming from the interruption of blood flow. Several clinical trials are now investigating nitrite as a therapy for conditions such as heart attack, ruptured aneurysm, sickle cell pain crisis and cardiac arrest.

Nitrite acts as the body’s reserve for nitric oxide, which turns on chemical pathways that relax blood vessels. Delivering nitric oxide directly into the body is expensive and hard to control. Unlike nitric oxide, whose lifetime in the body is a few seconds, nitrite is stable and stored in the body’s tissues and can be delivered in a variety of ways. It is converted into nitric oxide under conditions when the body needs it: lack of blood or oxygen. In addition, sodium nitrite has been used as part of a cyanide antidote kit. This means that safety data on large doses of nitrite in critically ill people is available.

In a 2005 paper published in the Journal of Clinical Investigation, Lefer and colleagues showed that nitrite can reduce damage to the hearts of mice after a simulated heart attack. More recently, assistant professor John Calvert and Lefer have shown that internally generated and stored nitrite is an important way that exercise protects the heart from a heart attack.

Some blood pressure studies underway in Europe have participants consume large amounts of beet juice as their source of nitrate, which is then converted to nitrite in the body.

A wave of public concern about nitrite and its relative nitrate in the 1970s focused on their presence in cured meats and their ability to form nitrosamines, which can be carcinogenic. Subsequent investigation showed that actually, most of the nitrite and nitrate in the average adult’s diet come from vegetables such as broccoli and spinach, and that antioxidants such as vitamin C can prevent nitrosamine formation.

Nathan Bryan, a speaker at the conference from UT-Houston, was featured in a recent television news story about herbal supplements designed to boost nitrite in the body.

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Study: Regular aerobic exercise and prevention of drug abuse relapse

Exercise provides health benefits

Researchers at Emory University and the University of Georgia have received funding from the National Institutes of Health to study the neurobiological mechanisms for how regular aerobic exercise may prevent drug abuse relapse. The grant is for $1.9 million over the next five years.

David Weinshenker, PhD, associate professor of human genetics, Emory School of Medicine, is a co-principal investigator on the project.

David Weinshenker, PhD

“This research will provide new insight into how regular exercise may attenuate drug abuse in humans,” Weinshenker says “More importantly, it may reveal a neural mechanism through which exercise may prevent the relapse into drug-seeking behavior.”

During the study, Weinshenker and UGA co-investigator Philip Holmes, professor of psychology in the Franklin College of Arts and Sciences, will measure exercise-induced increases of the galanin gene activity in the rat brain.

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