Common allergy drug reduces obesity and diabetes in mice
08/07/2009

BOSTON, MA – Researchers at Brigham and Women’s Hospital (BWH) have found that two common over-the-counter allergy medications may reduce both obesity and type 2 diabetes in mice. The medications, called Zaditor and cromolyn, stabilize a population of inflammatory immune cells called mast cells. This research appears in the July issue of Nature

Online PR News – 07-August-2009 – – Guo-Ping Shi, a biochemist from the Department of Medicine at BWH, began to suspect such a connection when, in a previous study, he found mast cells present in a variety of inflammatory vascular diseases.
Mast cells are immune cells that facilitate healing in wounded tissue, primarily by increasing blood flow to the site. However, in certain conditions mast cells build up to levels far beyond what the body needs. As a result these cells become unstable and eventually, like punctured trash bags, leak molecular “garbage” into the tissue. This can result in chronic inflammation that causes asthma and certain allergies.
As Shi and colleagues discovered, mast cells were far more abundant in fat tissue from obese and diabetic humans and mice than they were in normal weight fat tissue. This led to an obvious question: by regulating mast cells, could we then control the symptoms?
To find out, Shi and colleagues took a group of obese and diabetic mice and, for a period of two months, treated them with either ketotifen fumarate (also called Zaditor) or cromolyn, both over-the-counter allergy drugs.
“We knew from published research that both cromolyn and Zaditor help stabilize mast cells in people suffering from allergy or asthma,” said Shi. “It’s almost as if the drugs place an extra layer of plastic on the ripped trash bag. So it seemed like a logical place to begin.”
The mice were divided into four groups. The first was the control group; the second group was simply switched to a healthy diet; the third was given cromolyn or ketotifen fumarate; and the fourth was both given the drug and switched to a healthy diet.
While symptoms of the second group improved moderately, the third group demonstrated dramatic improvements in both body weight and diabetes. The fourth group exhibited nearly 100 percent recovery in all areas.
To bolster these findings, Shi and colleagues then took a group of mice whose ability to produce mast cells was genetically impaired. Despite three months of a diet rich in sugar and fat, these mice neither became obese nor developed diabetes.
“The best thing about these drugs is that we know it’s safe for people,” says Shi. “The remaining question now is: Will this also work for people?”
Shi now intends to test cromolyn and ketotifen fumarate on obese and diabetic non-human primates.
The research was funded by grants from the National Institutes of Health.

Using Math To Take The Lag Out Of Jet Lag
Researchers at Brigham and Women's Hospital and the University of Michigan have developed a software program that prescribes a regimen for avoiding jet lag using timed light exposure.

FOR IMMEDIATE RELEASE
PRLog (Press Release) – Jul 03, 2009 – Researchers at Brigham and Women's Hospital and the University of Michigan have developed a software program that prescribes a regimen for avoiding jet lag using timed light exposure. The method is described in an article published June 19 in the open-access journal PLoS
Computational Biology.

Traveling across several times zones can cause an individual to experience jet lag, which includes trouble sleeping at night and difficulty remaining awake during the day. These effects largely reflect de-synchronization between the body's internal time clock and local environmental cues.

The program, which seeks to re-synchronize the body with its new environment, considers inputs like background light level and the number of time zones traveled. Then, based on a mathematical model, the program gives users exact times of the day when they should apply countermeasures such as bright light to intervene and reduce the effects of jet lag.

Timed light exposure is a well known synchronization method, and when used properly, this intervention can reset an individual's internal clock to align with local time. The result is more efficient sleep, a decrease in fatigue, and an increase in cognitive performance. Poorly timed light exposure can prolong the re-synchronization process. Using their computational method, researchers simulated shifting sleep-wake schedules and the subsequent light interventions for realigning internal clocks with local time. They found that the mathematical computation resulted in quicker design of schedules and also predictions of substantial performance improvements. They were able to show that the computation provided the optimal result for timing light exposure to reduce jet lag symptoms.

"Using this computation in a prototyped software application allows a user to set a background light level and the number of time zones traveled to obtain a recommendation of when to expose a subject to bright light, such as the bright lights sometimes used to treat Seasonal Affective Disorder" said lead-author Dennis Dean. "Although this method is not yet available to the public, it has direct implications for designing schedules for jet lag, shift-work, and extreme environments, such as in space, undersea or in polar regions."

"This work shows how interventions can cut the number of days needed to adjust to a new time zone by half," said co-author Daniel Forger.

The next phase of this research includes the addition of interventions such as naps, caffeine and melatonin to help the process of realigning the internal body clock while reducing decreased performance experienced during travel across time zones.

To learn more about why sleep matters, the science behind it and how to improve your sleep, visit http://healthysleep.med.harvard.edu/.

FINANCIAL DISCLOSURE: The work described in this article was supported by US AFOSR F49620-95-1-0388 and F49620-95-1-0388, NASA Cooperative Agreement NCC 9-58 with NSBRI HPF-00405, NIH M01-RR02635 and NIH R01-NS36590. EBK is also supported by NIH K02-HD045459. DBF is an AFOSR Young investigator. DAD is also supported by T32 HL07901-10. The funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.

About Brigham and Women's Hospital:-
Brigham and Women's Hospital (BWH) is a 777-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery system. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. In July 2008, the hospital opened the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on a diversity of human diseases and is at the forefront of personalized medicine. BWH has approximately 900 scientific investigators and more than $450 million in research support, more than 50 percent of which comes from the NIH. BWH is also home to major landmark population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative, which have provided important information on diet and lifestyle risk factors for common chronic diseases. For more information about BWH, please visit http://www.brighamandwomens.org/