Here's something in our local rag about silver ions and other forms of
silver.  More grist for our mill.

Trem


There May Be a Silver Lining for Patients With Infections

BY FRANK D. ROYLANCE THE BALTIMORE SUN

Silver. It's not just for jewelry anymore.

Colorado company Nexxion Corp. is hoping a thin film of silver oxide on
medical devices will help prevent many of the 2 million infections that
patients acquire in hospitals every year.

The revival of silver - an ancient germ-fighter - is an effort to combat
"nosocomial" infections, which strike 5 percent to 10 percent of hospital
patients, according to the U.S. Centers for Disease Control and Prevention.

The cost of treating them averages $6,000 per patient, or as much as $10
billion a year.

It's been estimated that nosocomial infections contributed to the deaths of
88,000 Americans in 1995, according to the CDC. Most had immune systems
weakened by age, underlying disease, or medical or surgical treatment. If
Nexxion wins approval from the Food and Drug Administration, the company
says its silver coatings on such devices as catheters or artificial knees
would kill most of the Staphylococcus aureus, E. coli and other bacteria
that the devices frequently carry into a patient's body, preventing
infection and allowing wounds to heal normally. The technology would also
reduce the use of antibiotics, and help curb the development of dangerous
antibiotic resistance among infectious organisms.

"There are no bacteria known to be resistant to silver or silver oxide,"
said Dan Storey, Nexxion's chief technical officer, who spoke this week in
Baltimore at the annual March meeting of the American Physical Society.

Silver isn't new to the war against infection, Storey said. Roman soldiers
put silver coins in water to purify it. Silver sutures were developed in the
mid 19th century to reduce wound infection. And doctors for generations put
silver nitrate drops into the eyes of newborns to prevent blindness caused
by gonorrhea contracted from their mothers during childbirth.

The development of antibiotics in the 1940s pushed silver treatments aside,
but concerns about the evolution of antibiotic-resistant organisms have
revived interest in them.

Not just any silver will do. "In the past, it's been just pure silver,"
Storey said. "It's somewhat effective, but it's not very strong in its pure
form.



..What we’re doing new is we are creating a silver oxide which is inherently
an unstable molecule," he said. When these molecules get into the body, they
split into a silver ion and an oxygen "free radical," both of which are
toxic to microorganisms.

"This is like a one-two punch," Storey said.

A conventional antibiotic typically works by attaching itself to a receptor
on the surface of the microbe, and using that route to enter and kill or
cripple it. But in time, some of the bacteria will mutate in a way that
prevents the drug from working at that receptor anymore. The defensive trait
is passed along and a new, antibiotic-resistant strain of bacterium is born.

The silver ion, however, is taken directly into the cell, where it
interferes with a variety of cell functions and components, including DNA,
killing the organism. "The physical structure of the DNA cannot change such
that it rejects this ion," Storey said. "If it were to mutate, it would kill
itself, because it wouldn't be able to replicate."

The real challenge for Nexxion was to develop a way to coat medical devices
with silver that would preserve its effectiveness without damaging the
devices.

The solution was something called "low-temperature ionic plasma deposition."
Simply put, the silver is vaporized, passed through an extremely hot oxygen
plasma, and deposited on the medical devices es in a flexible film a
half-micron Iron deep.

"We are able to deposit it - pretty much on anything," Storey said.

Nexxion says testing shows - that its silver coatings reduce bacterial
populations by factors of 100,000 to 1 million. "So we are a thousand times
better than what is considered 'antimicrobial' in the industry," Storey
said.

The effects can be extended from a few days to as long as 28 days, if
needed, before the body absorbs all the silver and eliminates it, he said.

But silver has its drawbacks. In sufficient concentrations, silver ions are
toxic to healthy human cells. Tests of another company's artificial heart
valve with a silver component were ended in 2001 after the silver caused
adjacent heart cells to die, loosening the valve.

To avoid similar problems with Nexxion's products, Storey said, "we just had
to tune it down to find the sweet spot where we're killing bacteria but
not killing the human cells."

The silver coating still can cause inflammation, he said. - But "that
actually seems to speed healing, because when you cause inflammation, it
rushes blood and nutrients to that site and helps regrowth." It's a very
promising but i problematic field, according to Dr. Dennis G. Maki, a
professor of medicine and head of infectious diseases at the University
of Wisconsin Medical School. He is not associated with Nexxion.

Silver oxide coatings have i been investigated for 20 years, he said, but
"they really had no benefit at all. They didn't work."

"Although the silver ion is very bactericidal, maintaining it in its ionic
state is very difficult," he said. "You don't get enough silver ion to kill
the bacteria."

Storey said Nexxion's product will work better than previous silver coatings
because the deposition process produces a more unstable and therefore more
available and effective silver ion.

The company is testing three silver-coated devices on animals. Human trials
are not required because Nexxion's product - a metal  is not considered a
drug. And it's being proposed for use on devices already approved by the FDA
for human use.





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