Possible new blood test to diagnose heart attacks

Monday 23 September 2013

Islamabad, Sep 24 (Newswire): Loyola University Chicago Stritch School of Medicine researchers are reporting a possible new blood test to help diagnose heart attacks. In the Journal of Molecular and Cellular Cardiology, researchers report that a large protein known as cardiac myosin binding protein-C (cMyBP-C) is released to the blood following a heart attack.

"This potentially could become the basis for a new test, used in conjunction with other blood tests, to help diagnose heart attacks," said senior author Sakthivel Sadayappan, PhD.

"This is the beginning. A lot of additional studies will be necessary to establish cMyBP-C as a true biomarker for heart attacks."

Sadayappan is an assistant professor in the Department of Cell and Molecular Physiology at Loyola University Chicago Stritch School of Medicine. First author is Suresh Govindan, PhD, a postdoctoral researcher in Sadayappan's lab.

Between 60 and 70 percent of all patients who complain of chest pain do not have heart attacks. Many of these patients are admitted to the hospital, at considerable time and expense, until a heart attack is definitively ruled out.

An electrocardiogram can diagnose major heart attacks, but not minor ones. There also are blood tests for various proteins associated with heart attacks. But most of these proteins are not specific to the heart. Elevated levels could indicate a problem other than a heart attack, such as a muscle injury.

Only one protein now used in blood tests, called cardiac troponin-I, is specific to the heart. But it takes at least four to six hours for this protein to show up in the blood following a heart attack. So the search is on for another heart attack protein that is specific to the heart.

The Loyola study is the first to find that cMyBP-C is associated with heart attacks. The protein is specific to the heart. And it may be readily detectable in a blood test because of its large molecular size and relatively high concentration in the blood.

Researchers evaluated blood samples from heart attack patients. They also evaluated rats that had experienced heart attacks. They found that in both humans and rats, cMyBP-C was elevated significantly following heart attacks.

Sadayappan said cMyBP-C is a large assembly protein that stabilizes heart muscle structure and regulates cardiac function.  During a heart attack, a coronary artery is blocked, and heart muscle cells begin to die due to lack of blood flow and oxygen.

As heart cells die, cMyPB-C breaks into fragments and is released into the blood. "Future studies," Sadayappan and colleagues wrote, "would determine the time course of release, peak concentrations and half life in the circulatory system."

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Stem cells, potential source of cancer-fighting T cells

Islamabad, Sep 24 (Newswire): Adult stem cells from mice converted to antigen-specific T cells -- the immune cells that fight cancer tumor cells -- show promise in cancer immunotherapy and may lead to a simpler, more efficient way to use the body's immune system to fight cancer, according to Penn State College of Medicine researchers.

"Cancer immunotherapy is a promising method to treat cancer patients," said Jianxsun Song, Ph.D., assistant professor, microbiology and immunology. "Tumors grow because patients lack the kind of antigen-specific T cells needed to kill the cancer. An approach called adoptive T cell immunotherapy generates the T cells outside the body, which are then used inside the body to target cancer cells."

It is complex and expensive to expand T cell lines in the lab, so researchers have been searching for ways to simplify the process. 

Song and his team found a way to use induced pluripotent stem (iPS) cells, which are adult cells that are genetically changed to be stem cells.

"Any cell can become a stem cell," Song explained. "It's a very good approach to generating the antigen-specific T cells and creates an unlimited source of cells for adoptive immunotherapy."

By inserting DNA, researchers change the mouse iPS cells into immune cells and inject them into mice with tumors. After 50 days, 100 percent of the mice in the study were still alive, compared to 55 percent of control mice, which received tumor-reactive immune cells isolated from donors.

Researchers reported their results and were featured as the cover story in a recent issue of the journal Cancer Research.

A limitation of this potential therapy is that it currently takes at least six weeks for the iPS cells to develop into T cells in the body. In addition, potential side effects need to be considered. iPS cells may develop into other harmful cells in the body.

Researchers are now studying how to use the process in human cells. Other researchers on this paper are Fengyang Lei, and Rizwanul Haque, Department of Microbiology and Immunology; Lynn Budgeon and Neil D. Christensen, Ph.D., Department of Pathology, Penn State College of Medicine.

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Common stimulant may speed recovery from general anesthesia

Islamabad, Sep 24 (Newswire): Administration of the commonly used stimulant drug methylphenidate (Ritalin) was able to speed recovery from general anesthesia in an animal study conducted at Massachusetts General Hospital (MGH).

The report, appearing in the October issue of Anesthesiology, is the first demonstration in mammals of what could be a safe and effective way to induce arousal from general anesthesia.

While there are drugs to counteract many of the agents used by anesthesiologists -- such as pain killers and muscle relaxants -- until now there has been no way to actively reverse the unconsciousness induced by general anesthesia.

"Currently at the end of a surgical procedure, the anesthesiologist just lets general anesthetic drugs wear off, and the patient regains consciousness," says Emery Brown, MD, PhD, of the MGH Department of Anesthesia, Critical Care and Pain Medicine, senior author of the paper. "If these findings can be replicated in humans, it could change the practice of anesthesiology -- potentially reducing post-anesthesia complications like delirium and cognitive dysfunction in pediatric and elderly patients."

General anesthesia has been an essential tool of medicine since it was first demonstrated at the MGH in 1846, but only in recent years have researchers begun to investigate the neurobiology of general anesthesia and to understand exactly how anesthetic drugs produce their effects. Studies by Brown and other scientists have shown that the state of general anesthesia is actually a controlled and reversible coma and bears little similarity to natural sleep. Several neurotransmitter pathways in the brain are known to be generally involved in arousal, but which ones may contribute to recovery from general anesthesia is not yet known.

The stimulant drug methylphenidate, widely used to treat attention-deficit hyperactivity disorder, is known to affect arousal-associated pathways controlled by the neurotransmitters dopamine, norepinephrine and histamine.

The current study was designed to see whether methylphenidate could stimulate arousal in rats receiving the anesthetic drug isoflurane. The first experiments showed that animals receiving intravenous methylphenidate five minutes before discontinuation of isoflurane recovered significantly faster than did rats receiving a saline injection.

Another experiment showed that methylphenidate induced signs of arousal -- movement, standing up, etc. -- in animals continuing to receive isoflurane at a dose that would have been sufficient to maintain unconsciousness. EEG readings taken during that experiment showed that brain rhythms associated with arousal returned within 30 seconds of methylphenidate administration. 
Giving a drug that interferes with the dopamine pathway blocked the arousal effects of methylphenidate, supporting the role of that pathway in the drug's effects.

"Our results tell us that, even though we don't yet know the precise mechanisms underlying general anesthesia, we can overcome its effects by activating arousal pathways," says Ken Solt, MD, of the MGH Department of Anesthesia, Critical Care and Pain Medicine, the paper's lead and corresponding author.

"Instead of the traditional paradigm of reversing drug actions at the molecular level, methylphenidate acts at the level of neural circuits to overcome the effects of isoflurane. Since we still know very little about the pathways involved in general anesthesia, we will be testing the actions of methylphenidate with other anesthetic agents to see if these arousal effects are broadly applicable."

Brown adds, "More precise ways to induce and control the arousal process may lead to strategies that help patients recover from coma. We also found that methylphenidate increased respiration in anesthetized animals, which could help rescue patients who receive too much sedation for simple procedures.

And the ability to safely reduce the time patients spend in the operating room -- which can cost between $1,000 and $1,500 an hour -- could translate into significant savings in health costs."

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