Gene editing reverses Huntington's in mouse model

This is a concrete example, not yet clinical, of what can be done with CRISPR/Cas9 gene Read more

Urine tests for prostate cancer could reduce biopsies

Urine RNA tests could reduce the number of biopsies by giving a preview of a cancer's aggressiveness. Featuring Martin Sanda and Carlos Read more

Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

blood pressure

Flow mediated dilation

On Friday, researchers from Emory Clinical Cardiovascular Research Institute demonstrated a test for how much blood vessels adjust to changes in blood flow. This test is known as “flow-mediated dilation” or FMD. A blood pressure measurement cuff is tightened on the arm for five minutes, restricting blood flow.

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ECCRI investigator Salman Sher, MD demonstrates flow-mediated dilation

When the cuff is released, blood flow increases, but how much the arm’s main artery expands depends on the endothelium – the lining of the artery — and its ability to respond to nitric oxide, which is induced by the increased flow. Researchers monitor the artery’s expansion by ultrasound.

ECCRI co-director Arshed Quyyumi and his colleagues at Emory have extensive experience using the FMD test. Impaired endothelial function is an early stage in the process of atherosclerosis.

The FMD test is relatively non-invasive, in that no catheter probe is necessary. However, practitioners need practice and careful study design to ensure accuracy, ECCRI investigator Salman Sher explained. Posture, time of day and whether the patient has eaten can all affect the results.

Lab Land asked Sher (seated in the photo) whether the effect was similar to the common experience of sleeping on an arm and having it turn numb, followed by “pins and needles” when the pressure is relieved. This feeling actually comes from nerve compression. Read more

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Football metabolomics

Following on the recent announcement of the Atlanta Hawks training center, here’s a Nov. 2015 research paper from Emory’s sports cardiologist Jonathan Kim, published in Annals of Sports Medicine and Research.

Jonathan Kim, MD

Kim and colleagues from Emory Clinical Cardiovascular Research Institute studied blood samples from 15 freshman football players at Georgia Tech before and after their first competitive season. The researchers had the help of metabolomics expert Dean Jones. Kim has also previously studied blood pressure risk factors in college football players.

On average, football players’ resting heart rate went down significantly (72 to 61 beats per minute), but there were no significant changes in body mass index or blood pressure. The research team observed changes in players’ amino acid metabolism, which they attribute to muscle buildup.

This finding may seem obvious, but imagine what a larger, more detailed analysis could do: start to replace locker room myths and marketing aimed at bodybuilders with science. This was a small, preliminary study, and the authors note they were not able to assess diet or nutritional supplementation. Read more

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More on Alzheimer’s-blood pressure link

Emory’s Alzheimer’s Disease Research Center recently announced a grant that will support studies on the connections between blood pressure regulation and Alzheimer’s disease. It focuses on the roles of the renin-angiotensin system, the targets of common blood pressure medications, and endothelial cells, which line blood vessels.

Research on that theme is already underway at Emory. Malu Tansey is leading a large project funded by the National Institute on Aging ($3.4 million) with a similar title: “Inflammation and Renin-Angiotensin System Dysfunction as Risk Factors for Alzheimer’s Disease.” Co-investigators are Felicia Goldstein and Lary Walker at Emory and Christopher Norris at the University of Kentucky.

Both studies build on evidence that molecules that control blood pressure and inflammation also drive progression of Alzheimer’s disease, including work by Emory’s Whitney Wharton and Ihab Hajjar. They had found in an observational study that people who take medications targeting the renin-angiotensin system have a lower risk of progressing from mild cognitive impairment to Alzheimer’s.

Wharton is gearing up to test that idea more directly in an interventional study with the generic angiotensin receptor blocker telmisartan. This study is part of a “Part the Cloud” initiative supported by the Alzheimer’s Association.

Tansey’s project has started bearing fruit in an animal model of Alzheimer’s, according to this Keystone meeting report from Alzforum. Last summer, her graduate student Kathryn Macpherson described initial findings on the effects of an anti-inflammatory (anti-TNF) agent, which also has positive effects in a Parkinson’s model, and her plans to investigate the effects of high-sugar, high-fat diet.

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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.

Read more

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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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