By Denise Trunk
GAINESVILLE, Fla. - A breakdown in brain cell communication may contribute to the most common biochemical cause of mental retardation, University of Florida scientists have discovered.
The process is akin to a baseball game gone bad. Imagine if a pitcher were joined by six players simultaneously winding up on the mound. Crouched behind home plate, the single catcher would soon be overwhelmed. Even if the coach sent in teammates to catch the extra balls, confusion would reign on the field.
UF researchers, writing in the journal Brain, identified an analogous situation in the brains of mice with a version of the hereditary disorder phenylketonuria, or PKU: A flood of an amino acid found in nearly all foods bombards certain brain cells, drowning out their ability to communicate properly and potentially interfering with normal brain development.
Scientists have long known that babies born with PKU lack or are deficient in the enzyme that converts the amino acid phenylalanine into a usable form. The amount of the amino acid in the blood builds to toxic levels, ultimately causing severe brain disorders, including mental retardation and seizures. Researchers have been less clear on precisely how that torrent of phenylalanine interferes with brain function.
"Despite tremendous progress in the understanding of the molecular basis of PKU, the mechanisms of how the brain is negatively affected by high levels of phenylalanine has not been known," said Anatoly Martynyuk, Ph.D., an assistant professor of anesthesiology and neuroscience at UF's College of Medicine and the McKnight Brain Institute. "This is a new and original approach to explain the cellular mechanisms of brain dysfunction in PKU."
The findings could someday lead to a treatment for the disease in people and provide insight into other neurological disorders with similar symptoms, Martynyuk said.
Every state screens newborns for PKU. Those with the condition are restricted to an arduous all-liquid diet that eliminates or greatly reduces protein intake, at least through adolescence and possibly throughout their lives. Caught early, brain damage can be avoided and people with the condition can lead normal lives, except for having to adhere to a protein-free liquid diet.
UF researchers discovered that in the brains of mice with PKU, levels of phenylalanine soar to six times higher than levels found in healthy mice. The excess phenylalanine interferes with a key brain cell chemical messenger, glutamate, which plays a crucial role in brain development and function.
The changes in that cellular communication system may at least partially explain the brain disorders associated with PKU, Martynyuk said.
Martynyuk said UF researchers are now examining how the process contributes to seizures in patients with PKU who are not treated with a special diet.
"Based on our findings, we hypothesize that the changes in the brain can be caused not only by higher levels of phenylalanine, but also by withdrawal of phenylalanine," Martynyuk said. "For example, sequential decreases in phenylalanine levels caused by variations in diet will facilitate glutamate system activity in the brain and can destabilize the entire system. In such conditions, seizures are likely."
UF researchers said related research suggests phenylalanine and its derivatives might someday be used to treat other brain disorders in which an abnormal glutamate system plays a role, such as stroke and schizophrenia.
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Florida veterinarians become first in U.S. to perform electric shock treatment to correct heart abnormality in horses
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By Sarah Carey
GAINESVILLE, Fla. - Borrowing from a Canadian veterinarian's unique expertise, University of Florida veterinarians recently became the first in the United States believed to have successfully performed intracardiac electrical conversion of a common arrhythmia in horses that causes irregular and fast heartbeats.
Two horses received the procedure in March 2005, including an Ocala thoroughbred named Captain who was part of a training exercise conducted for UF veterinarians by the individual who developed the technique, Canadian veterinarian Kim McGurrin, D.V.M. McGurrin developed the cutting-edge technique over the last four years along with her mentor, Peter Physick-Sheard, B.V.Sc., at the University of Guelph in Ontario, Canada.
Captain's arrhythmia had been treated medically several times but without success, said Mel Valley Farm owner-caretaker Carl Stump. Now, however, Captain appears to be doing well, Stump said.
"He is now training at a local place here in Ocala, so he is back to work," Stump said.
McGurrin said the intracardiac electrical conversion technique was developed to offer new treatment options for atrial fibrillation.
"It is excellent that UF is now capable of performing this procedure," McGurrin said. "We have applied this technique on more than 50 horses, including 44 client-owned horses referred from the states. Most horses have returned to performance and we now consider this procedure routine."
Amara Estrada, D.V.M., an assistant professor of veterinary cardiology at UF's College of Veterinary Medicine, and her colleague, Darcy Adin, D.V.M., were both involved in the recent UF procedure. Estrada said the cardiac abnormality for which the procedure is used is "an important arrhythmia for many reasons."
"Probably it is most important to horse owners and trainers of race horses because it causes poor performance and poor racing," Estrada said. "But certainly pet horses develop the condition as well."
It is also the most common arrhythmia in horses, occurring in 1 to 2 percent.
Estrada said irregular or fast heartbeat, also known as atrial fibrillation, causes a decrease in cardiac output, negatively impacting a horse's performance.
The disease is said to be frustrating to both horse owners and veterinarians because medical therapy frequently has to be administered many times and often has serious side effects.
"Typical medical treatment has consisted of antiarrythmic drugs given orally or intravenously, but the drugs can have fairly significant side effects, including toxicity," said Steeve Giguère, D.V.M., Ph.D., an associate professor of equine medicine at UF.
The UF veterinarians had heard of McGurrin and were aware that intracardiac electrical conversion technology was now being performed in horses at the University of Guelph routinely with "great success," Giguère said.
The procedure, which takes about two hours, involves surgically threading two catheters through veins in the horse's neck into the heart's right atrium and the pulmonary artery. Echocardiography is used to guide the placement of the catheters.
"Once the catheters are in the correct location, a short shock is delivered to 'reset' the atria and terminate the fibrillation, thus establishing a normal rhythm," Estrada said.
The equipment used to administer the shock is a biphasic defribrillator, the same technology used in human emergency medicine to treat cardiac arrhythmias.
"Most horses with atrial fibrillation do not have underlying heart disease," Giguère said. "So if you can restore their normal sinus rhythm, they usually return to their previous level of performance."
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