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Monday, November 10, 2014

CDMRP: Neuroinflammation in Gulf War Illness



SOURCE: Congressionally Directed Medical Research Program (CDMRP), U.S. Army Medical Research and Materiel Command, U.S. Department of Defense.  Published Nov. 10, 2014

http://cdmrp.army.mil/gwirp/research_highlights/14Lasley_OCallaghan_highlight.shtml


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Posted November 10, 2014

Steve Lasley, Ph.D., University of Illinois College of Medicine at Peoria
James O'Callaghan, Ph.D., Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health

Drs. Steve Lasley and James O'CallaghanGulf War Illness (GWI) is a multi-symptom disorder with features characteristic of "sickness" behavior including cognitive impairment, fatigue, depression, sleep disruption, muscle and joint pain, and gastrointestinal and dermatological problems.

Typically, sickness behavior is the normal manifestation of an inflammatory response to infection or injury and one that resolves with restoration of homeostasis. In GWI such symptoms persist, and research suggests this may be due to heightened and chronic inflammation of the nervous system following a mild toxic exposure to any of a number of neurotoxic compounds.

In work supported by a Fiscal Year 2008 Gulf War Illness Research Program (GWIRP) Investigator-Initiated Research Award, Dr. Steve Lasley at the University of Illinois College of Medicine at Peoria, along with collaborator Dr. James O'Callaghan at the Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health, set out to characterize chronic neuroinflammation using an animal model of GWI. To produce the initial elevated level of inflammation in mice, Drs. Lasley and O'Callaghan and their teams gave animals low doses of an acetylcholinesterase inhibitor called diisopropyl fluorophosphate (DFP). In these experiments this chemical was used as a nerve gas surrogate: At higher doses it can cause neuronal damage by abolishing the normal signal transmission at connections involving one type of nerves. This results in excess nerve firing, possibly leading to seizures and nerve system damage due to overstimulation.

Using this procedure, the researchers found that exposure to a single dose of DFP that did not produce overt signs of toxicity in the animals did result in inflammation in the brain, which was measured by monitoring inflammatory cytokine levels and microglial activation. Furthermore, the observed neuroinflammatory response was exacerbated when animals were given the stress hormone corticosterone (CORT) prior to DFP exposure. This was an unexpected finding because CORT is generally thought to be an immunosuppressive hormone secreted by the body to prevent damage from the body's own inflammatory responses. Instead of reducing the initial neuroinflammatory response to DFP, prior exposure to CORT was found to "prime" the immune system of DFP-treated animals to mount an exaggerated response. This phenomenon could also be produced after brief CORT exposure using another inflammogen called lipopolysaccharide. Giving mice occasional doses of CORT over time (as a person might naturally experience in a war theater as a result of day-to-day stresses) was found to maintain this pro-inflammatory state for 180 days, which is the approximate human equivalent of 20 years.

Dr. O'Callaghan further discovered that the tetracycline-like antibiotic minocycline was able to reduce both DFP-induced and CORT-enhanced neuroinflammation. Minocycline is a U.S. Food and Drug Administration-approved antibiotic that is known to exert immune suppressive, anti-inflammatory effects in addition to its antibiotic properties. Furthermore, minocycline is also known to cross the blood-brain barrier, allowing it to suppress inflammation in the brain. These characteristics, along with the findings by Dr. O'Callaghan, suggest that minocycline may be an effective treatment option for veterans suffering from GWI. The GWIRP is supporting continuation of research on the immune system priming by CORT and possible treatments using minocycline through Gulf War Illness Consortium grants to Boston and Nova Southeastern Universities, which are expected to conduct human treatment trials.

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Friday, November 7, 2014

NY TIMES: "More Than 600 Reported Chemical Exposure in Iraq, Pentagon Acknowledges"



SOURCE:  New York Times, C.J. Chivers reporting, Nov. 6, 2014

http://www.nytimes.com/2014/11/07/world/middleeast/-more-than-600-reported-chemical-weapons-exposure-in-iraq-pentagon-acknowledges.html?smprod=nytcore-iphone&smid=nytcore-iphone-share&_r=0



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PLAY VIDEO|13:15

Chemical Secrets of the Iraq War

Chemical Secrets of the Iraq War

The United States went to war in Iraq expecting to destroy an active weapons of mass destruction program. Instead, it found only remnants of chemical arms built in close collaboration with the West.
 Video by Mac William Bishop and C.J. Chivers on Publish Date October 14, 2014. Photo by Roberto Schmidt/Agence France-Presse — Getty Images.
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More than 600 American service members since 2003 have reported to military medical staff members that they believe they were exposed to chemical warfare agents in Iraq, but the Pentagon failed to recognize the scope of the reported cases or offer adequate tracking and treatment to those who may have been injured, defense officials say.
The Pentagon’s disclosure abruptly changed the scale and potential costs of the United States’ encounters with abandoned chemical weapons during the occupation of Iraq, episodes the military had for more than a decade kept from view.
This previously untold chapter of the occupation became public after an investigation by The New York Times revealed last month that while troops did not find an active weapons of mass destruction program, they did encounter degraded chemical weapons from the 1980s that had been hidden in caches or used in makeshift bombs.
The Times initially disclosed 17 cases of American service members who were injured by sarin or sulfur mustard agent. And since the report was published last month, more service members have come forward, pushing the number who were exposed to chemical agents to more than 25. But an internal review of Pentagon records ordered by Defense Secretary Chuck Hagel has now uncovered that hundreds of troops told the military they believe they were exposed, officials said.
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The new and larger tally of potential cases suggests that there were more encounters with chemical weapons than the United States has acknowledged and that other people — including foreign soldiers, private contractors and Iraqi troops and civilians — may also have been at risk.
Having not acted for years on that data, the Pentagon says it will now expand outreach to veterans. One first step, officials said, includes a toll-free national telephone hotline for service members and veterans to report potential exposures and seek medical evaluation or care.
Phillip Carter, who leads veterans programs at the Center for a New American Security, called the Pentagon’s failure to organize and follow up on the information “a stunning oversight.” Paul Rieckhoff, founder and executive director of Iraq and Afghanistan Veterans of America, said the military must restore trust by sharing information.
“We need total transparency and absolute candor,” Mr. Rieckhoff said, and noted the military’s poor record in releasing information about its use in Vietnam of Agent Orange, a chemical defoliant linked to an array of health problems, and in sharing data about troops’ presumed chemical exposures and other medical and environmental risks during and soon after the 1991 Persian Gulf war.
Military officers said the previously unacknowledged data was discovered when, at Mr. Hagel’s prodding, the Army’s Public Health Command examined its collection of standardized medical-history surveys, known as post-deployment health assessments, which troops filled out as they completed combat tours.
The assessments included the following question: “Do you think you were exposed to any chemical, biological and radiological warfare agents during this deployment?” For those who answered Yes, the forms provided a block for a brief narrative explanation.
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Document: In Army Health Surveys, Troops Report Chemical Weapons Exposure in Iraq 

Col. Jerome Buller, a spokesman for the Army surgeon general, said Thursday that the review showed that 629 people answered yes to that question and also filled in the block with information indicating chemical agent exposure.
Each person who answered the questionnaire would have received a medical consultation at the end of their combat tour, Colonel Buller said.
Why the military did not take further steps — including compiling the data as it accumulated over more than a decade, tracking veterans with related medical complaints, or circulating warnings about risks to soldiers and to the Department of Veterans Affairs — remained unclear.
Before post-deployment assessments were reviewed, Colonel Buller said, the Public Health Command had already expanded its search for potential victims and intended to examine the medical records of all troops assigned to units that the Army has belatedly acknowledged handled or were attacked with chemical weapons.
These include three Army explosive ordnance disposal companies and B Company, First Battalion, 14th Infantry, he said.
Veterans said this unit list was incomplete and would inevitably grow as the military accounted for other high-risk troops, including those on route-clearance duties in areas where chemical roadside bombs were repeatedly found, or chemical warfare troops who served in so-called technical escort units, which were assigned to collect and analyze the old chemical weapons.
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Document: Exchange Between Hagel and Congress on Chemical Weapons Exposure in Iraq 

Nonetheless, the new data has prompted the Public Health Command to take further steps, Colonel Buller said.
These will include identifying all veterans who reported a possible chemical exposure, gathering their medical records, contacting them for a structured interview and perhaps inviting them for a medical exam.
He said the Department of Defense had also revived a telephone line, 1-800-497-6261, for veterans to notify the Pentagon that they may have been exposed. The phone line, he said, had previously been used for veterans reporting Gulf War-related illnesses.
Immediate reactions among exposed service members and veterans’ advocates mixed cautious appreciation with skepticism.
“It’s too little, too late,” said Jordan Zoeller, a former Army sergeant who served in a platoon that was exposed to sulfur mustard agent as soldiers destroyed buried chemical artillery shells near Taji in 2008.
Mr. Zoeller was medically retired after developing a series of health problems, including asthma and psoriasis. He said his breathing trouble began within weeks of the chemical episode, though he is not sure its onset was related to mustard agent because the Army denied that he had been exposed and did not examine his claims.
Photo
A portion of the 114 chemical projectiles discovered in December 2006, awaiting disposal on Forward Operating Base Brassfield-Mora. One of them leaked mustard agent onto the forearm of a Navy explosive ordnance disposal technician.CreditThe New York Times 
“No one ever believed me,” he said. “They were like, ‘Oh, that never happened._ ”
He said at one point after he returned to the States and coughed up blood and lost consciousness, a regimental surgeon agreed to look into the episode. Nothing came of it, he said.
Another veteran, a Navy explosive ordnance disposal technician who remains on active duty, said he was burned on the left forearm in December 2006 when handling 114 American-designed M110 mustard shells at a bomb-makers’ weapons cache near Samarra.
He said that after the mustard agent splashed on his arm he quickly rinsed it away by squirting it repeatedly with solution from IV bags. The mustard agent still caused a long patch of redness that took weeks to heal and left scarring, he said.
The sailor, who asked that his name be withheld, said when he sought treatment at Forward Operating Base Brassfield-Mora, the Army doctor was not interested.
An officer in the unit to which he was assigned — a battalion from the 505th Parachute Infantry Regiment, he said — issued what he called “a gag order” that forbade him to discuss that he had found chemical shells.
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Document: Medical Records of U.S. Casualties of Iraq’s Chemical Weapons 

The sailor’s post-deployment health survey, which he provided to The Times, shows he reported the exposure again as he left Iraq in late 2007.
The attending caregiver did not recommend further care, but noted the previous order prohibiting mention of the incident. The patient, he wrote, “was instructed not to discuss due to mission classification.”
Cmdr. Ryan Perry, a Navy spokesman, said that the sailor had discussed the exposure with the Navy in recent days and that any previous order of silence was unacceptable.
“We in no way condone the silencing of any of our service members,” he said, “and are greatly encouraged that this sailor took the step of reaching out to the Navy so we can get him the medical attention he needs.”
While exposure to nerve or blister agents can carry long-term health risks, veterans, medical officers and exposure victims said that it was impossible to analyze the new data immediately and predict how many troops who reported exposure would have suffered medical problems. They said it could also be difficult to establish how closely medical complaints might be linked to exposure.
They noted that many of the troops’ encounters with chemical agents could have been brief and minimal, as that of a turret gunner in a vehicle passing briefly through an area where a chemical shell had been used in a makeshift bomb.
Moreover, not all chemical agents were alike. The nerve agents found in Iraq after the United States invaded in 2003 were much less potent than when manufactured decades ago, according to people involved in many of the chemical weapons recoveries in Iraq. Iraqi mustard agents tended to be of higher quality and far more stable, they said.
Nonetheless, Mr. Carter and Mr. Rieckhoff said that the latest number was probably understated, and that the military should not rely on people who reported chemical weapons exposures to determine the scope of the problem.
It should look deeper, Mr. Carter said, at symptoms, such as troops who reported rashes, breathing difficulties or tremors.

Tuesday, November 4, 2014

CoQ10 Helps Veterans Battle Gulf War Illness Symptoms with 80% Success Rate


Note that this treatment research was funded through the Gulf War Illness Congressionally Directed Medical Research Program (CDMRP).  

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SOURCE:  UC-San Diego Press Release, Nov. 3, 2014


News Release

Date: November 03, 2014 

Coenzyme Q10 Helps Veterans Battle Gulf War Illness Symptoms 

Eighty percent of treated veterans improved physical function 

Roughly one-third of the 700,000 United States troops who fought in the 1990-1991 Persian Gulf War have subsequently developed a distinct set of chronic health problems, dubbed Gulf War illness. Their symptoms, from fatigue, muscle pain and weakness to decreased cognitive function and gastrointestinal and skin problems, persist decades after the conflict. 
In a study published in the Nov. 1 issue of Neural Computation,  researchers at the University of California, San Diego School of Medicine report  that a high quality brand of coenzyme Q10 (CoQ10) – a compound commonly sold as a dietary supplement – provides  health benefits to persons suffering from Gulf War illness symptoms.  
Forty-six United States Gulf War veterans participated in the randomized, double-blind, placebo-controlled study. Each veteran had been diagnosed with Gulf War illness. 
“Gulf War illness is not the same as post-traumatic stress disorder or traumatic brain injury, signature illnesses of later deployments, which are caused by psychological and mechanical injury, respectively,” said Beatrice Golomb, MD, PhD, professor of medicine at UC San Diego School of Medicine and principal investigator on the study. “Evidence instead links Gulf War illness to chemical exposures, such as pesticides or pills given to soldiers to protect them from possible nerve agents. These chemicals can damage mitochondria, which generate the energy our cells need to do their jobs. When these powerhouses of the cells are disrupted, it can produce symptoms compatible with those seen in Gulf War illness.”  
The connection to chemical and toxin exposures is fortified by evidence of mitochondrial problems in affected veterans, said Golomb, as well as evidence showing those veterans who became ill are significantly more likely than others to harbor genetic variants that render their enzymes less effective at detoxifying these chemicals. 
CoQ10 is a fat-soluble antioxidant made by the body to support basic cell functions, including directly assisting mitochondrial energy production. Over a course of three and a half months, the veterans in the study received a pill form of either CoQ10 or a placebo. Researchers found 80 percent of those who received 100mg of CoQ10 had improvement in physical function. The degree of improvement correlated to the degree in which CoQ10 levels in the blood increased.
The researchers reported that Gulf War illness symptoms like headaches, fatigue with exertion, irritability, recall problems and muscle pain also improved.
“The statistical significance of these benefits, despite the small sample size, underscores the large magnitude of the effects,” Golomb said. “Mounting evidence suggests findings in Gulf War illness are relevant to toxin-induced health problems in the civilian sector, so what we learn by studying health challenges of these veterans, will likely benefit others.”  
Golomb and colleagues are seeking additional funding to test a more complete “mitochondrial cocktail,” which combines CoQ10 with additional nutrients that support cell energy and reduce oxidative damage to cells.  
Co-authors include:  Matthew Allison, Sabrina Koperski, Hayley J. Koslik and Janis B. Richie, all at UC San Diego; and Sridevi Devaraj, Baylor College of Medicine/ Texas Children’s Hospital and Health Center.
Funding support for this research came, in part, from the Department of Defense
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Media contact: Michelle Brubaker, 619-543-6163, mmbrubaker@ucsd.edu

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Journal Reference:
  1. Beatrice A. Golomb, Matthew Allison, Sabrina Koperski, Hayley J. Koslik, Sridevi Devaraj, Janis B. Ritchie. Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind StudyNeural Computation, 2014; 26 (11): 2594 DOI: 10.1162/NECO_a_00659