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Despite the lack of evidence linking phthalates such as DEHP to diseases in
humans, the chemicals have nevertheless become a pariah, according to Galland.
Thus, the European Union in particular has taken the assault on phthalates very
seriously. And because many U.S. medical device manufacturers do not want to
produce separate product lines for Europe and America, they intend to follow the
path of least resistance and replace phthalates with nonphthalate substitutes,
such as citrates, adipates, trimellitates, benzoates, polymeric adipates, and
terephthalate. Due to a totally different and benign behavior in rodent
toxicology, terephthalates are not considered phthalates by the regulatory
agencies governing medical devices in either the United States or Europe,
Galland explains.
“The goal in choosing an alternative plasticizer is to have it mimic all of the
properties exhibited by DEHP, the current industry workhorse,” Galland says. The
new chemicals should resemble as closely as possible DEHP’s chemical structure,
toxicology, solubility, migration, crazing, sterilizability, mechanical
properties, processing properties, design, economics, and current market
penetration. “However,” Galland adds, “replacing DEHP is not easy because it has
been the perfect PVC plasticizer for medical devices for more than 40 years.
While its solubility in aqueous media could perhaps be improved upon, some of
the prime replacement candidates are unfortunately even more water-soluble. And
the more soluble a plasticizer is in the liquids flowing through medical device
tubing into the body, the more it will wind up in the patient's bloodstream,
becoming a matter of relative toxicology.”
For more information on phthalates, see the article “Know your Plasticizers: A
New Study on Plasticizer Migration.”
http://www.qmed.com/mpmn/medtechpulse/medtechs-tackle-replacing-workhorse-plasticizer
Plastic Injection Protects Mouse Hearts After Attack
The discovery was a happy accident. It turns out that an injection of
microscopic tags made of a plastic-like polymer can help limit tissue damage
after a heart attack in mice. The hope is that it could one day help treat this
and other conditions in humans.
The hunt to find a therapy that shuts down inflammatory monocytes – a kind of
immune cell that can damage the body after a heart attack and in other illnesses
- has been long and elusive, says Stephen Miller at Northwestern University in
Illinois.
He and his team have found a way to use microparticles made of the biodegradable
polymer PLGA to tag these monocytes in mice. This triggered the monocytes to
move away from inflamed sites to the spleen, where they are destroyed. It seems
other immune cells are left unscathed.
One existing use for the microparticles, which are just 1/200th the width of a
hair, is for laboratory imaging, to label and trace cells. 'Daniel Getts was
using them in this way to study how inflammatory monocytes travelled from the
bloodstream to the brain of mice with West Nile virus, where they damage tissue.
Lucky mistake
By mistake, one batch of microparticles became negatively charged. Instead of
seeing the majority of his infected mice die from brain inflammation, as
expected, Getts found that monocytes had bound themselves to his charged
microparticles and moved into the spleen.
"It was a total accident that we discovered this," says Getts. He found that 60
per cent of the infected mice survived.
The negatively-charged microparticles had bound to a receptor protein on the
surface of inflammatory monocytes called "MARCO." This protein usually detects
and sticks to negatively charged regions on pathogens, dying cells and other
debris in the blood. Binding this particular receptor, the researchers suspect,
signals the monocyte to go to the spleen, where cargo and cell are destroyed.
Getts says it was a natural move to try tagging monocytes in this way in
diseases in which they damage tissue.
Innovative approach
Controlling inflammation after a heart attack was a priority. During the first
couple of days after an attack, monocytes can target oxygen-deprived heart
muscle, damaging it further. Mice injected with microparticles 12 hours after an
attack had heart lesions half the size of those who did not receive therapy. The
hearts of treated mice also pumped better.
The microparticles helped reduced spinal inflammation in mice with a disease
similar to human multiple sclerosis, making their paralysis less severe. Those
with irritable bowel syndrome similarly showed reduced inflammation of the
intestinal lining. And those with kidney injuries had signs of better organ
function, suggesting the tags might be effective after organ transplants.
Miller says the team hopes to begin human clinical trials to test the therapy
for heart attack this year.
"The approach is innovative," says Nick Giannoukakis, a pathologist at the
University of Pittsburgh Medical Center in Pennsylvania. But he adds that a
better understanding of events after MARCO binding would be helpful.
Journal reference: Science Translational Medicine, DOI:
10.1126/scitranslmed.3007563
http://www.newscientist.com/article/dn24902-plastic-injection-protects-mouse-hearts-after-attack.html.
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