TRENDS AND ISSUES

Cardio Vascular System: Stress-Reduction Therapy May Help Heart Disease Patients

Reducing anxiety cuts heart attacks, deaths and other cardiovascular events,
research suggests

MONDAY, Jan. 24 (HealthDay News) -- A stress management program based on

cognitive behavioral therapy may reduce the risk of heart attack, stroke and death in
patients with heart disease, Swedish researchers report.

About 30 percent of heart attacks may be linked to "psychosocial factors,"

including chronic stressors such as poverty or emotional problems, such as depression
and hostility, the authors note in the Jan. 24 issue of the Archives of Internal Medicine.
"Psychological treatment appears to prevent recurrent [cardiac] events at least as
effective as many of today's established pharmacological treatments," said lead
researcher Dr. Mats Gulliksson, from the Family Medicine and Clinical Epidemiology
Section at Uppsala University Hospital.

For the study, Gulliksson's group randomly assigned 362 men and women with
heart disease to usual care and cognitive behavioral therapy or usual care with no
therapy. Patients in therapy underwent 20 two-hour sessions over a year. Usual care
included medications to lower blood pressure and cholesterol or to prevent blood clots,
Gulliksson said.

The premise of CBT is that by changing the way you think about something, you
can help yourself feel or behave better. The study program included five key
components with specific goals -- education, self-monitoring, skills training, cognitive
restructuring and spiritual development -- and focused on stress management,
specifically reducing the experience of daily stress, time urgency and hostility.
Over almost eight years of follow-up, the CBT group had 23 deaths, 69 cardiovascular
events, and 41 heart attacks. However, among those who did not take part in therapy,
25 died, 77 had any type of cardiovascular event and 51 suffered heart attacks, the
researchers found.

That works out to 41 percent fewer deaths and heart-related events and 45
percent fewer heart attacks among those in the CBT group, compared with patients who
did not receive therapy, they add.

Those who went to the most therapy sessions had a further reduction in risk, the
researchers note. "The higher the attendance rates, the lower the risk," Gulliksson said.
"The psychological treatment had a clear impact beyond the already known beneficial
effects of conventional treatments to prevent recurrent events," Gulliksson said. "The
effects were similar for men and women," he added. Exactly how the stress
management strategies protect the heart is a question for future research, he noted.
It's possible that the better outcomes relate to long-term participation (six to 12 months
at least) in a group designed to alter behavior, the authors say. Perhaps by decreasing
emotional and behavioral reactivity, people can alleviate some of the burden placed on
the cardiovascular system, they add.

"The positive results suggest that cognitive behavioral therapy intervention based
on stress management should be added to secondary prevention programs and offered
to all coronary heart disease patients," Gulliksson said. The therapy is also inexpensive
and without side effects, he added.

But at least one expert remained unconvinced that the health benefits noted in
the study were related to the CBT therapy.

"We know from many trials that people in intervention trials tend to get better
care," said Dr. Robert Myerburg, a professor of medicine and cardiology at the
University of Miami Miller School of Medicine.

What isn't clear from the study is whether the therapy patients kept to their
medication regimen more consistently than the non-therapy patients, he said. For
example, the study authors don't show whether blood pressure and cholesterol were
better controlled in the therapy group than in the non-therapy group, Myerburg said.

"The question is, is this a direct effect or a nonspecific effect of an intervention

where we know that people tend to 'behave better' in terms of their outcomes and
therapies?" he said.

Despite his skepticism, Myerburg doesn't see a downside if a patient wants to try
cognitive behavioral therapy.

"What I say to patients, as with all these unproven therapies, is as long as they
are not doing harm I have no objection," he said.

Chocolate to combat heart diseases

Chocolate to combat heart diseases (Think stock photos/Getty Images)

Chocolate could be combating heart disease and conferring other major health benefits
within five years.

Researchers are scouring the genome of the tree theobroma cacao to find ways
of enhancing the health benefits of cocoa beans produced by the plant.

They took two years to unlock the genetic code of the tree and now hope to use
the information it contains to improve the quality, flavour and nutritional value of the
beans, which are used to produce chocolate.
 They believe they can boost the levels of compounds known as flavonols in the
beans, reports the Telegraph .

Flavonols have been found in recent research to improve blood pressure and
have beneficial effects on the cardiovascular system.

Howard-Yara Shapiro, professor of environmental sciences at the University of

California, US, said: "The idea is that this is something that will become the norm -
healthy fats, high levels of flavonols."

"Chocolate will become something quite different in 10-15 years and we are on
that track now," he said, according to a University of California release.

"It is not something we can deliver tomorrow, but maybe in five years we can."

Shapiro persuaded Mars Incorporated to fund the $10 million project to decode
the genome, with the help of computer firm IBM, which analysed the data, and the US
Department of Agriculture.

Shapiro and his team are now searching the cocoa tree's 34,997 genes in the
attempt to select key traits that will improve the plants and the chocolate that comes
from them.

Blood : Researchers Inch Closer to Unlocking Potential of Synthetic Blood

Science Daily (Jan. 11, 2011) — A team of scientists has created particles that closely
mirror some of the key properties of red blood cells, potentially helping pave the way for
the development of synthetic blood.

The new discovery -- outlined in a study appearing in the online Early Edition of
the Proceedings of the National Academy of Sciences during the week of Jan. 10, 2011
-- also could lead to more effective treatments for life threatening medical conditions
such as cancer.

University of North Carolina at Chapel Hill researchers used technology known

as PRINT (Particle Replication in Non-wetting Templates) to produce very soft hydrogel
particles that mimic the size, shape and flexibility of red blood cells, allowing the
particles to circulate in the body for extended periods of time.

Tests of the particles' ability to perform functions such as transporting oxygen or

carrying therapeutic drugs have not been conducted, and they do not remain in the
cardiovascular system as long as real red blood cells.
However, the researchers believe the findings -- especially regarding flexibility -- are
significant because red blood cells naturally deform in order to pass through
microscopic pores in organs and narrow blood vessels. Over their 120-day lifespan, real
cells gradually become stiffer and eventually are filtered out of circulation when they can
no longer deform enough to pass through pores in the spleen. To date, attempts to
create effective red blood cell mimics have been limited because the particles tend to be
quickly filtered out of circulation due to their inflexibility.

Beyond moving closer to producing fully synthetic blood, the findings could affect
approaches to treating cancer. Cancer cells are softer than healthy cells, enabling them
to lodge in different places in the body, leading to the disease's spread. Particles loaded
with cancer-fighting medicines that can remain in circulation longer may open the door
to more aggressive treatment approaches.

"Creating particles for extended circulation in the blood stream has been a
significant challenge in the development of drug delivery systems from the beginning,"
said Joseph DeSimone, Ph.D., the study's co-lead investigator, Chancellor's Eminent
Professor of Chemistry in UNC's College of Arts and Sciences, a member of UNC's
Lineberger Comprehensive Cancer Center and William R. Kenan Jr. Distinguished
Professor of Chemical Engineering at N.C. State University. "Although we will have to
consider particle deformability along with other parameters when we study the behavior
of particles in the human body, we believe this study represents a real game changer
for the future of nanomedicine."

Chad Mirkin, Ph.D., George B. Rathmann Professor of Chemistry at

Northwestern University, said the ability to mimic the natural processes of a body for
medicinal purposes has been a long-standing but evasive goal for researchers. "These
findings are significant since the ability to reproducibly synthesize micron-scale particles
with tunable deformability that can move through the body unrestricted as do red blood
cells, opens the door to a new frontier in treating disease," said Mirkin, who also is a
member of President Obama's Council of Advisors on Science and Technology and
director of Northwestern's International Institute for Nanotechnology.

UNC researchers designed the hydrogel material for the study to make particles
of varying stiffness. Then, using PRINT technology -- a technique invented in
DeSimone's lab to produce nanoparticles with control over size, shape and chemistry --
they created molds, which were filled with the hydrogel solution and processed to
produce thousands of red blood cell-like discs, each a mere 6 micrometers in diameter.

The team then tested the particles to determine their ability to circulate in the
body without being filtered out by various organs. When tested in mice, the more flexible
particles lasted 30 times longer than stiffer ones: the least flexible particles disappeared
from circulation with a half-life of 2.88 hours, compared to 93.29 hours for the most
flexible ones. Stiffness also influenced where particles eventually ended up: more rigid
particles tended to lodge in the lungs, but the more flexible particles did not; instead,
they were removed by the spleen, the organ that typically removes old real red blood
cells.

The study was led by Timothy Merkel, a graduate student in DeSimone's lab, and
DeSimone. The research was made possible through a federal American Recovery and
Reinvestment Act stimulus grant provided by the National Heart, Lung and Blood
Institute, part of the National Institutes of Health (NIH). Support was also provided by
the National Science Foundation, the Carolina Center for Cancer Nanotechnology
Excellence, the NIH Pioneer Award Program and Liquidia Technologies, a privately held
nanotechnology company developing vaccines and therapeutics based on the PRINT
particle technology. DeSimone co-founded the company, which holds an exclusive
license to the PRINT technology from UNC.

Other UNC student, faculty and staff researchers who contributed to the study
are Kevin P. Herlihy and Farrell R. Kersey from the chemistry department; Mary Napier
and J. Christopher Luft from the Carolina Center for Cancer Nanotechnology
Excellence; Andrew Z. Wang from the Lineberger Center; Adam R. Shields from the
physics department; Huali Wu and William C. Zamboni from the Institute for
Pharmacogenomics and Individualized Therapy at the Eshelman School of Pharmacy;
and James E. Bear and Stephen W. Jones from the cell and developmental biology
department in the School of Medicine.

Blood: Protein Helps Determine When Red Blood Cells Die

Science Daily (Aug. 7, 2007) — The accumulation of high levels of oxidants in

red blood cells dramatically decreases their lifespan and is associated with anemia.

Little was known about the molecular regulation of the response to oxidants in
red blood cells, but in a study appearing in the August issue of the Journal of Clinical
Investigation the protein FoxO3 is now shown to be required for mouse red blood cells
to control their levels of oxidants and it is therefore probable that Foxo3 regulates the
lifespan of these cells.

In the study, Saghi Ghaffari and colleagues from the Mount Sinai School of
Medicine, New York, show that the induction of high levels of oxidants in mice lacking
Foxo3 caused them to die rapidly.

Red blood cells from these mice expressed fewer proteins able to scavenge the
oxidants and had a shorter lifespan than red blood cells from normal mice. Importantly,
treatment of the cells with an antioxidant increased the lifespan of the red blood cells
lacking Fox03.

A lack of Foxo3, and therefore high levels of oxidants, also decreased the rate of
red blood cell development and led the authors to posit that it might be possible to
exploit these functions of Fox03 to increase the lifespan and rate of development of red
blood cells.

However, as Harvey Lodish, from the Whitehead Institute for Biomedical

Research, notes in his accompanying commentary these data highlight "the importance
of determining both the direct targets of Fox03 and its own regulation in helping us
understand how a red blood cell lacking a nucleus knows exactly when to die."

NERVOUS SYSTEM : Altered Cell Metabolism Has Role in Brain Tumor Development

ScienceDaily (Jan. 31, 2011) — Scientists at Duke Cancer Institute have

discovered that genetic mutations found in brain tumors can alter tumor metabolism.
This work could help lead to new designs for anti-cancer drugs based on the unique
properties of these tumors.

"Malignant glioma appears to be at least two large subclasses of diseases -- one

that involves mutations in the IDH1 and IDH2 genes and one that doesn't," said Hai
Yan, M.D., Ph.D., an associate professor in the Duke Department of Pathology who led
a collaborative group of researchers to conduct the study. "The IDH mutation can serve
as a biomarker to help single out individuals who are likely to have better outcomes and
who might then receive a particular type of treatment based on their tumor IDH mutation
status."

"What we and other researchers are learning now is that certain changes in cellular
metabolism are probably a hallmark of cancer," said Yan, who works in the Preston
Robert Tisch Brain Tumor Center at Duke and the Pediatric Brain Tumor Foundation
Institute.

The study was published in the journal Proceedings of the National Academy of
Sciences Early Edition the week of Jan. 31.

Two years ago, work by Yan and his colleagues showed that a mutation that
disrupts the isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) genes was common in
some types of incurable brain tumors, including astrocytomas, oligodendrogliomas, and
glioblastomas. Their work suggested that these tumors require the gene to go awry at
some point during cancer development. Though key IDH discoveries have been made
around the world, a reason that IDH gene mutations could have such a profound
influence on brain cancer has remained elusive.

In the current study, Yan's group solved the connection to metabolism. The IDH1
and IDH2 genes are known to play an important role in cell metabolism -- the
conversion of nutrients into energy and into building blocks to manufacture new cells.
The researchers examined concentrations of hundreds of metabolites, including sugar,
protein, and fat molecules, in cancer cells that they were able to grow in their laboratory.
Technological improvements in the past five years -- the science of metabolomics --
have made it possible for scientists to simultaneously look at hundreds or thousands of
such metabolites to learn what happened in cells with the mutation.

The technology revealed that more than 100 metabolites had altered
concentrations in cells with the defective IDH1 or IDH2 genes compared to cells without
the defective genes.
 One very common metabolite in the human brain -- N-acetyl-aspartyl-glutamate
-- was found to be 50 times less common in cells that had that IDH1 mutation compared
to those that did not, said Zach Reitman, a student pursuing combined M.D. and Ph.D.
degrees in the Medical Scientist Training Program at Duke. "The fact that defective
genes can alter the metabolism of cancer cells could mean that altering cellular
metabolism is an important step in brain tumor development."

Ivan Spasojevic, Ph.D., assistant director and manager of the Duke Clinical
Pharmacology Laboratory, said, "We devised a brand new method to confirm that some
of these changes were also present in patients with brain tumors. This approach gave
us confidence that what we saw in metabolomics studies of cancer cells in petri dishes
was what was really happening in patients," Spasojevic said.

Tumors were removed as part of the patients' normal treatment course, and the
tumor tissue was analyzed with patient consent.

"The study emphasized that cellular metabolism could potentially be an 'Achilles

heel' for brain tumors, and it points to several promising avenues for future research into
new treatments for brain tumors in particular," said Genglin Jin, Ph.D., a key author and
postdoctoral research fellow in Yan's lab.

Other authors of the study included Yiping He, M.D., Ph.D., and Darell Bigner,
M.D., Ph.D., who are also with the Duke Cancer Institute, the Preston Robert Tisch
Brain Tumor Center at Duke and the Pediatric Brain Tumor Foundation Institute, and in
the Department of Pathology. Other authors work at the Ludwig Center for Cancer
Genetics and Therapeutics and the Howard Hughes Medical Institute at Johns Hopkins
Kimmel Cancer Center.
Funding came from American Cancer Society, the Pediatric Brain Tumor
Foundation Institute, the Virginia and D.K. Ludwig Fund for Cancer Research, and
National Institutes of Health grants. Yan, Bigner and two Johns Hopkins (JHU) scientists
reported being eligible for royalties received by JHU on sales of products related to
research on IDH1, under licensing agreements between the JHU and Beckman Coulter.

Nerve Cell Molecule Has Antidepressant Effect; Animal Study May Lead to More
Effective Treatments for Depression

ScienceDaily (Nov. 16, 2010) — Mice that lack a molecule involved in regulating
nerve cell signaling are more active and resilient to stressful situations, a new study
shows. The research was presented at Neuroscience 2010, the annual meeting of the
Society for Neuroscience, held in San Diego.

Mice lacking the molecule -- known as Cdk5 -- exhibited the same behaviors
seen in mice given antidepressant drugs.

"We immediately realized that these mice could teach us something important
about depression and that we could use them to study new pathways that might serve
as targets to treat the disease," said senior author James Bibb, PhD, of the University of
Texas Southwestern Medical Center, who directed the study.

When dopamine and serotonin, brain chemicals involved in mood regulation, act
at brain cells, a "wave" of the signaling molecule cyclic adenosine monophosphate
(cyclic AMP) is generated. Normally, another molecule, phosphodiesterase, breaks
down the cyclic AMP. However, Bibb and his colleagues discovered that
phosphodiesterase did not do its job -- the wave of cyclic AMP did not stop -- in mice
that lacked Cdk5. Without Cdk5, the mice behaved with more resilience to stress and
showed strong antidepressant-like behavior. The discovery that Cdk5 regulates
phosphodiesterases opens up new opportunities to target them.

"Our hope is that the conceptual advances these findings represent will
contribute to the development of new depression therapeutics," Bibb said.

Research was supported by the National Institute of Mental Health, the National
Institute on Drug Addiction, and the Department of Psychiatry at the University of Texas
Southwestern Medical Center.

SKELETAL :Going from Strength to Strength: Effects of Growth Hormone on Muscle

ScienceDaily (Oct. 1, 2010) — Growth hormone is used to treat children's growth

disorders and has been used by some sports men and women to promote muscle
growth and regeneration. This is because it coordinates skeletal muscle development,
nutrient uptake, and nutrient utilization. It is not clear, however, which of these effects
are direct and which are indirectly mediated via growth hormone induction of the protein
IGF-1.

Now, however, a team of researchers, led by Thomas Clemens, at Johns

Hopkins University School of Medicine, Baltimore, has used mice engineered to lack in
their skeletal muscle either the molecule to which growth hormone binds or the
molecule to which IGF-1 binds to show that growth hormone control of skeletal muscle
development is dependent on IGF-1, whereas its control of nutrient uptake is
independent of IGF-1.

The authors hope that with additional work, these results will guide more
informed use of growth hormone or growth hormone analogs for promoting muscle
development and reducing muscle loss.

Diffuse Idiopathic Skeletal Hyperostosis Causes Dysphagia in Older Patients

ScienceDaily (Apr. 9, 2010) — Diffuse idiopathic skeletal hyperostosis (DISH) is

a common but often unrecognized systemic disorder observed mainly in elderly people.
All papers related to DISH demonstrate a consistent and marked increase of the
disease with advancing age. Various local structural lesions such as oropharyngeal
tumors, vascular pathologies, retropharyngeal abscesses, and anterior cervical
osteophytes may lead to mechanical esophageal dysphagia.

A research article to be published on April 7, 2010 in the World Journal of

Gastroenterology addresses this question. A research team led by Dr. Berrin Karadag
reported a case of a geriatric patient with diffuse idiopathic skeletal hyperostosis.
This study concluded that DISH should be considered an important, although rare,
cause of dysphagia among older adults. However, it should not be accepted as the
cause of dysphagia until all other causes have been ruled out.