Research Roundup
Editor’s Note: The following information on MCG research is abridged from articles posted at www.mcg.edu/news.
Bacteria pirate mechanism to infiltrate cells
In an article published Jan. 23 in Proceedings of the National Academy of Sciences, corresponding author Dr. Yehia Daaka, MCG professor and Distinguished Chair in Oncologic Pathology Bacteria, discusses the mechanisms bacteria and viruses utilize to get inside cells and grow.
He and colleagues at Howard Hughes Medical Institute and Duke University Medical Center have found that the short-lived, ubiquitous gas, nitric oxide, is a primary enabler for receptors and pathogens to make this move. The scientists hope identifying this role of nitric oxide provides a new target for better methods to prevent infections.
Dr. Daaka, who studies receptor-signaling, likens receptors to television antennae that control relay of signals from outside the cell to inside by turning on or off. Although there are no known receptors that have the job of triggering a bad result in the body, receptors that are ‘on’ too much may end up instructing the cell to malfunction. “The hypothesis is that in cancer, for example, the receptors get stuck on ‘on’,” said Dr. Daaka, a Georgia Cancer Coalition Distinguished Cancer Scholar.
Receptor over-stimulation also helps explain why some drugs lose effectiveness over time.
The research was funded by the National Institutes of Health.
Genetics plays role in addiction relapse
Inbred strains of rats are helping behavioral neuroscientists understand a drug addict’s relapse behavior.
A study posted online Jan. 18 by Psychopharmacology is another piece of evidence that genetics play a role in relapse. Dr. Paul J. Kruzich, MCG behavioral neuroscientist and lead study author, is working to identify the relapse trigger to target ways to curb craving and subsequent relapse.
His studies focus on an area of the brain called the nucleus accumbens core, a target for drugs of abuse long considered a pleasure center. Drugs such as cocaine and methamphetamine stimulate release of dopamine in the nucleus accumbens. Dopamine is a neurotransmitter believed responsible for drug-related euphoria.
Glutamate, also released in the nucleus accumbens core, may play an equally important role in drug relapse, said Dr. Kruzich. Drugs such as cocaine appear to alter glutamate neurotransmission in the core, which may contribute to the rewiring of the brain that occurs with drug use.
Unfortunately, drugs that restore glutamate function also produce seizures, so scientists are looking for an indirect approach to restore the misdirected rewiring.
Treatment targets intracerebral hemorrhage
MCG is one of about 100 sites worldwide looking at whether patients with brain bleedscan benefit from rapid delivery of a factor that is part of the body’s natural clotting process.
Intracerebral hemorrhage accounts for up to 15 percent of the 750,000 strokes that occur annually in the United States, according Dr. Christiana E. Hall, MCG neurologist and a principal investigator on the NovoSeven® study. A large risk factor for this type of stroke is hypertension, common in the South.
The bleeding stretches and tears brain tissue, irreparably dissecting vital communication structures between brain cells. Patients can experience one-sided paralysis; coma; locked-in syndrome in which they are fully conscious but paralyzed from the eyes down; or death as blood spreads into brain tissue. Without treatment, bleeding and destruction may continue for several hours.
Treatments to date, including other clotting agents and surgery, generally have not improved outcomes, Dr. Hall said. A substance approved for hemophiliacs who develop antibodies to other treatments looks promising for intracerebral hemorrhage patients as well because it works at sites with tissue factor, which is exposed at sites of blood vessel injury.
Activated factor VIIa is a substance certain hemophilia patients may not have enough of. The Food and Drug Administration has approved it for hemophiliacs who develop antibodies to other treatments, Dr. Hall says. It looks promising for intracerebral hemorrhage patients as well because it works at sites where there is tissue factor, which is exposed at sites of blood vessel injury.
A study comparing NovoSeven®, or recombinant activated factor VIIa, to placebo will enroll 675 patients worldwide. Patients must be 18 or older and have a primary hemorrhage of almost any size and location. However, those who present with poor neurological exams, such as those already in a coma, cannot be enrolled.