New Thrombosis Treatments? Blood Clots Form Through Newly Discovered Mechanism

 

Science News

Edited

ScienceDaily (Dec. 15, 2009) — Polyphosphate from blood platelets plays a key role in inflammation and the formation of blood clots, scientists from the Swedish medical university Karolinska Institutet have shown. The study, which is presented in the scientific journal Cell, describes how this mechanism can be used in treatment.

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Blood clots are a common cause of myocardial infarction and stroke, and they arise when blood coagulates and clogs a blood vessel. Scientists have shown that the formation of a blood clot involves the aggregation of blood platelets and the formation of structures known as "fibrin threads," in combination with inflammation in the blood vessel. The molecular processes behind this, however, are only partially known.

A research group at Karolinska Institutet, in collaboration with American and European scientists, has discovered that an inorganic polymer, polyphosphate, plays a key role in both inflammation and the formation of blood clots. Experiments on mice and with patient plasma have shown that polyphosphate is released by blood platelets and activates Factor XII, a protein that scientists have previously shown to contribute to coagulation. Polyphosphate also activates inflammatory substances that contribute to leakage from the blood vessel, which is a characteristic feature of inflammation.

The scientists show also that certain enzymes, phosphatases, that break down polyphosphate can prevent both inflammation and the formation of blood clots in the blood vessels of mice. Thus the scientists believe that phosphatases can become the focus for a new type of treatment for blood clots and inflammation.

The discovery opens up opportunities for drug development, according to Dr Nicola Mutch from the University of Leeds who carried out the UK branch of the research.
"The challenge in designing treatments to reduce thrombosis is getting the balance right. We need to find an appropriate drug level or target which causes enough anticoagulation to prevent risk of heart attack or stroke but with minimal bleeding side effects," she explains, "Our work suggests polyphosphate or factor XII could be potential new targets, as neither seems to affect our ability to heal naturally, so drugs based on these molecules could offer a major improvement

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Journal Reference:

1. Felicitas Müller, Nicola J. Mutch, Wolfdieter A. Schenk, Stephanie A. Smith, Lucie Esterl, Henri M. Spronk, Stefan Schmidbauer, William A. Gahl, James H. Morrissey, and Thomas Renné. Platelet Polyphosphates Are Proinflammatory and Procoagulant Mediators In Vivo. Cell, Online 10 December 2009

New Clue Why Autistic People Don't Want Hugs

Science News

ScienceDaily (Feb. 11, 2010) — Why do people with fragile X syndrome, a genetic defect that is the best-known cause of autism and inherited mental retardation, recoil from hugs and physical touch -- even from their parents?

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New research has found in fragile X syndrome there is delayed development of the sensory cortex, the part of the brain that responds to touch, according to a study from Northwestern University Feinberg School of Medicine. This delay may trigger a domino effect and cause further problems with the correct wiring of the brain. Understanding how and when the function of the brain is affected in fragile X offers a target for a therapy to fix the incorrect development.

"There is a 'critical period' during development, when the brain is very plastic and is changing rapidly," said Anis Contractor, assistant professor of physiology at Feinberg and the lead investigator of the study. "All the elements of this rapid development have to be coordinated so that the brain becomes wired correctly and therefore functions properly."

The study will be published in the Feb. 11 issue of the journal Neuron.
Working with a mouse model of fragile X, Contractor found the development of synapses, the sites where neurons communicate with each other, was delayed in the sensory cortex.
"The critical period may provide a window during which therapeutic intervention can correct synaptic development and reverse some of the symptoms of the disease," Contractor said.
People with this syndrome have debilitating sensory as well as cognitive problems. "They have tactile defensiveness," Contractor explained. "They don't look in people's eyes, they won't hug their parents, and they are hypersensitive to touch and sound. All of this causes anxiety for family and friends as well as for the fragile X patients themselves. Now we have the first understanding of what goes wrong in the brain."

The sensory overload in people with fragile X results in social withdrawal, hyperarousal and anxiety. It shows up in early infancy and progressively worsens throughout childhood.
Fragile X syndrome is caused by a gene mutation in the X chromosome that interferes in the production of a protein called fragile X mental retardation protein (FMRP). That protein directs the formation of other proteins that build synapses in the brain. People with fragile X are missing FMRP. It's as if the foreman is missing on the brain's key construction site. Fragile X is so named because the X chromosome appears broken or kinked.

Boys are more severely affected by fragile X because they have only one X chromosome. Girls, who have two X chromosomes, are less affected by the defect.

Contractor and colleagues discovered the sensory cortex was late to mature by recording the electrical signals flowing through the animals' synapses. This provided a snapshot of when and how this part of the brain was developing. The ability of the brain to correctly process incoming information is based on the correct development of these synapses, he noted.

This is one of the first studies to show how synapses in this region are altered. "It starts to build a framework for how this part of the cortex actually develops," Contractor said. "Our next step is to work out what is going wrong. How does elimination of this gene FMR1 disrupt the normal developmental processes?"

The research was supported by the FRAXA Research Foundation and Autism Speaks.

Interventional Cardiologists Reduce Risk Of Stents By Magnetizing Endothelial Cells

Next Generation Of Heart Stents

December 1, 2008 — Interventional cardiologists used magnetic particles to accelerate the process of healing after the placement of a stent. To do this, they extract cells from the interior of a patient's blood vessels, cultivate them, and insert iron-based paramagnetic particles into the cells. When the cells are reintroduced to the blood, this attracts them to the magnetic coating on the stent, creating a film of living cells that promotes tissue healing and ultimately reduces the risk of blood clot formation.

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 A common heart problem may now have a magnetic solution. Researchers are using the laws of attraction to make heart stents that unclog blood vessels more safely.
A puppy named Cash is the newest member of Bob Stortron's family. At 68, Stortron says it's not too hard keeping up with him. A few years ago, it may have been more difficult. Stortron's heart was fading, and he had to have a stent put in. Stents reinforce blood vessel walls to keep vessels open and blood flowing.

"When you're talking about numbers of patients in the millions, 1 percent can add up to pretty large numbers," Gurpreet Sandhu, M.D., Ph.D., a cardiologist at Mayo Clinic in Rochester, Minn., said of those who need heart stents.

Normally, it takes weeks for endothelial cells to coat stents and blood vessels to heal. Now, interventional cardiologists are testing magnetic stents that attract those cells faster. First, cells are taken from the blood and tagged with iron microspheres. Then, a magnetic stent is threaded through the blood vessel. At last, tagged cells are sent through the blood vessels to see if they are attracted to the stent.
"This will hopefully mean fewer repeat procedures on patients and better quality of life for our patients," Dr. Sandhu said.
Dr. Sandhu says the technology speeds up healing to just days, requires fewer blood thinners and lowers the risk of blood clots.
Stortron says he couldn't ask for a better life, and he's content spending the rest of it enjoying his family.

"I hope I'm around for a long time, but I don't have control over that button," Stortron said.
WHAT MAKES MATERIALS MAGNETIC? Magnetism comes from the constant movement of charged electrons in atoms. As electrons swirl around an atom, they create an electrical current, and whenever electricity moves in a current, a magnetic field is created. So magnetism is a force between electric currents: two currents flowing in the same direction attract, while those pulling in opposite directions repel. The reason some materials are magnetic, while others are not, has to do with how the electrons are ordered. A magnet is an object made of magnetic materials; naturally occurring magnets are known as lodestones. Every magnet has at least one north pole and one south pole. In fact, if you take a bar magnet and break it into two pieces, each of the smaller pieces will still have a north and south pole. The Earth itself is a giant magnet with a north and south pole, which is why a magnetic compass's needle always points north/south.

WHAT ARE STENTS? A stent is essentially a small piece of metal "scaffolding" that pushes arterial plaque to the side and provides a framework to keep the blood vessel open so that the blood can flow freely through it. Stents have been used for many years to clear blockages in the arteries of the heart and neck.

The American Physical Society and the Materials Research Society contributed to the information contained in the TV portion of this report.