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‘Domino effect’ on genes triggered by steroids
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April 26, 2010  |  Posted in  Steroids Blog

'Domino effect' on genes triggered by steroidsCorticosteroids, the drugs that simultaneously deliver potent therapeutic effects and potentially severe adverse effects, can bring a remarkably complex ‘domino effect’ of genomic changes, as per a landmark paper by pharmaceutical scientists at University at Buffalo.

The paper was published online in the Journal of Pharmacology and Experimental Therapeutics (JPET).

From Sciencedaily.com:

What sets the work of the UB researchers apart from others is that they study pharmacodynamics, the time course of drug effects, on multiple genes and gene products.

“In our research, we try to look at the time frame of both positive and negative effects,” said Richard R. Almon, Ph.D., professor of biological sciences in the UB College of Arts and Sciences, co-author and Jusko’s partner in the work for more than a decade. “If we can find ways to increase the former and reduce the latter, then we can design better dosing regimens.”

Because of the severity of the side effects caused by steroids, more individualized dosing regimens are sorely needed, particularly for transplant patients, who usually have to take steroids for their lifetime to suppress their immune systems so that the transplanted organ is not rejected. Corticosteroids also are prescribed for patients suffering from rheumatoid arthritis, asthma, lupus and inflammatory bowel disease.

“When corticosteroids are prescribed for patients, many of them develop type 2 diabetes, muscle atrophy, atherosclerosis and osteoporosis,” said Almon.

“We don’t yet know how to turn up the drugs’ positive effects and turn down the others,” he said, adding that right now, corticosteroids are prescribed — as are most drugs — for an individual who is assumed to be average in all respects.

William J. Jusko, Ph.D., professor and chair of the Department of Pharmaceutical Sciences in the UB School of Pharmacy and Pharmaceutical Sciences and co-author on the paper, said this work offers the tools needed for better control over genomic changes that are triggered in vivo by corticosteroids or any other class of drugs.

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