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Tuesday, November 10, 2015

Emergency Estrogen for Trauma for men?

 On the battlefield for Trauma to our Wounded Soldiers and on the “battlefield” of life in our society perhaps very soon.
Breakthrough research suggests a female sex hormone (Estradiol( may be the key to saving lives on the battlefield, where between 2001 and 2011 more than 80 percent of potentially preventable U.S. war injury deaths resulted from blood loss.
The hormone shows the promise of prolonged survival despite massive loss of blood and could be carried in a small autoinjector for use.
The long path to this breakthrough for Chaudry, who is director of the Center for Surgical Research in the UAB School of Medicine, was prompted by a mistake; in 1997 he and postdoctoral fellow Rene Zellweger, M.D., received the wrong shipment of mice.
It is a fascinating story of how science advances by chance, happenstance, and sometimes laboratory errors
In a landmark step – after 19 years of research by Irshad Chaudry, Ph.D. – UAB has received a $10 million U.S. Department of Defense contract funded by the Combat Casualty Care Research Program, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD, to begin testing its potentially life-saving synthetic estrogen for safety in humans.
UAB has applied for patent protection for their synthetically produced EE-3-SO4. Beyond its battlefield potential, one important application could be domestic trauma patients, given that earlier E2 results that have shown reduced mortality and septicemia.
Also, EE-3- SO4 may have a third beneficial effect – treatment after traumatic brain injury. In experiments, the estrogen is able to reduce cerebral edema, increase brain blood flow, increase cognitive function and memory, and lessen brain cell death. Thus, EE-3-SO4 may prove to be a triple boon for trauma victims.
Trauma is the leading cause of U.S. deaths for people under 47 years of age, according to the federal Centers for Disease Control and Prevention. Because trauma hits all ages of people, it represents 30 percent of all U.S. life-years-lost each year, a far larger loss than cancer, 16 percent of all lost life-years, or heart disease, 12 percent.…/female-sex-hormone-may-save…
In 2005, the U.S. Defense Advanced Research Projects Agency, DARPA, announced a vital goal: finding a way to stretch the time that a severely wounded soldier with blood loss could stay alive. This would give the warfighter a better chance of reaching a field hospital for definitive surgical and medical care.
The agency held a competition with a simple and unequivocal criterion – produce a treatment that enables survival at least three hours after significant, almost universally fatal blood loss.
Because of the accidents and incidents in their a serenditous findings in their lab over many years, Chaudry and his colleagues had discovered that E2 could allow survival for three hours without any fluid resuscitation, and long-term survival if fluid resuscitation was provided after 3 hours.
The prolonged period of low blood pressure after blood loss significantly affects mitochondrial function, endoplasmic reticulum stress markers and inflammatory cytokine production, but E2 was able to diminish those changes.
Low blood pressure reduces the delivery of oxygen to tissues and to the mitochondria, which voraciously consume oxygen to produce energy in the form of ATP. T
Thus, oxygen deprivation is a burden for tissues and mitochondria under low blood flow conditions.
UAB came up with using a synthetic estrogen variant called ethinyl estradiol-3-sulfate, or EE-3-SO4 synthesized by a pharmaceutical company. that was microencapsulated within cyclodextrin to make it water soluble
Out of 10 initial Surviving Blood Loss programs, UAB was the only one that met the challenge of six-hour survival after 60 percent blood loss in the absence of fluid resuscitation.
DARPA’s six-hour aim was solely survival, but Chaudry has continued mechanistic studies of how EE-3-SO4 produces beneficial effects.
The estrogen appears to interact with the different types of estrogen receptors in all types of tissues in both men and women. Using selective estrogen-receptor antagonists or agonists for the different types of estrogen receptors, Chaudry’s research team continues to look at which type of receptor is important for EE-3-SO4action in different tissues.
Besides improved heart function, EE-3-SO4 appears to dilate blood vessels and speed the movement of fluid from the tissue compartment into the blood compartment (the interstitial fluid of the tissue compartment has about twice the volume compared to the average volume of blood in adult humans).
Lowering this resistance to improve blood flow to vital organs hails back to the great challenge to trauma recovery as "the body’s blood system is like a swamp after trauma, and anything
that turns the swamp into a running brook is the answer for treating shock."