News 27 mar 2009
MSU researcher links cholesterol
crystals to cardiovascular attacks
For the first time ever, a Michigan State
University researcher has shown cholesterol crystals can disrupt plaque in a
patient’s cardiovascular system, causing a heart attack or stroke. The findings by a
team led by George Abela, chief of the cardiology division in MSU’s College of Human
Medicine, could dramatically shift the way doctors and researchers approach cardiovascular
attacks. Abela’s findings appear in the April issue of the American Journal of
Cardiology. “Any time there is something completely new or unique in medical
research, it is met with healthy skepticism,” said Abela, who has been working with
cholesterol crystals since 2001. “But we have found something that can help
dramatically change how we treat heart disease.” What Abela and his team found is
that as cholesterol builds up along the wall of an artery, it crystallizes from a liquid
to a solid state and then expands. “As the cholesterol crystallizes, two things can
happen,” Abela said. “If it’s a big pool of cholesterol, it will expand,
causing the ‘cap’ of the deposit to tear off in the arterial wall. Or the
crystals, which are sharp, needle-like structures, poke their way through the cap covering
the cholesterol deposit, like nails through wood.”The crystals then work their way
into the bloodstream. It is the presence of this material, as well as damage to an artery,
that disrupts plaque and puts the body’s natural defense mechanism – clotting
– into action, which can lead to dangerous, if not fatal, clots. Abela and his team
studied coronary arteries and carotid plaques from patients who died of cardiovascular
attacks. When comparing their findings against a control group, they found evidence of
cholesterol crystals disrupting plaque.The breakthrough in discovering the crystals’
impact came after Abela and colleagues found a new way to preserve tissue after an
autopsy, using a vacuum dry method instead of an alcohol solution. The previous method
would dissolve the crystals and prevent researchers and doctors from seeing the impact.
Mayo Study Shows Simple Finger
Device May Help Predict Future Heart Events, Such as Heart Attack
Results of a Mayo Clinic study show that a
simple, noninvasive finger sensor test is "highly predictive" of a major cardiac
event, such as a heart attack or stroke, for people who are considered at low or moderate
risk, according to researchers. The noninvasive finger test device, called the EndoPAT by
Itamar Medical, measures the health of endothelial cells by measuring blood flow.
Endothelial cells line the blood vessels and regulate normal blood flow. Research has
shown that if the cells don't function properly — a condition called endothelial
dysfunction — it can set the stage for atherosclerosis (hardening of the arteries)
and lead to major cardiovascular health problems. Previously, there was no simple test for
endothelium function, says Amir Lerman, M.D., a cardiologist at Mayo Clinic and the senior
author of the study.
New study suggests Rx estrogen
delivery through the skin may show safety benefits as opposed to oral delivery
Transdermal delivery of estrogen therapy
available by prescription "seems not to alter" the risk of venous
thromboembolism (VTE), or blood clotting, in postmenopausal patients when compared to oral
delivery, a new study suggests. The study was conducted by researchers at NYU Langone
Medical Center and was published in the latest issue of Menopause: The Journal of the
North American Menopause Society.Prescription transdermal estrogen therapy is bioidentical
to estrogen produced by a woman's ovaries before menopause and delivered through the skin.
Transdermal estrogen is available in a variety of formulations which have been quality
controlled and approved safe and effective by the United States Food and Drug
Administration (FDA). The team at NYU Langone sought to determine the effects of delivery
of estrogen therapy on postmenopausal women. Blood obtained from 84 postmenopausal women
was tested for clotting activity before and after administration of oral or transdermal
estrogen for a period of eight weeks. Women with borderline clotting issues showed "a
significant acceleration" of clotting after oral estrogen therapy, but no significant
change after transdermal estrogen therapy. "Venous thromboembolic complications or
blood clots represent an established risk factor of estrogen therapy, and evidence is now
mounting that the route of estrogen administration influences this risk," said
researcher Lila Nachtigall, M.D., Director of the Women's Wellness Program at NYU.
"These new data on the safety of transdermal HT delivery may prove to be useful
information for postmenopausal women deciding whether to take estrogen therapy and whether
to take it orally or through the skin."
Scripps scientists find structure
of a protein that makes cancer cells resistant to chemotherapy
A research team at the Scripps Research
Institute has obtained the first glimpse of a protein that keeps certain substances,
including many drugs, out of cells. The protein, called P-glycoprotein or P-gp for short,
is one of the main reasons cancer cells are resistant to chemotherapy drugs. Understanding
its structure may help scientists design more effective drugs.The new research was
described in the March 27, 2009, issue of the journal Science. "This structure is an
important advance and we hope it is just the beginning of more breakthroughs for us,"
says the study's senior author Geoffrey Chang, an associate professor at Scripps Research.
"The structure is a nice tool for understanding how drugs are transported out of
cells by P-gp and for designing drugs to evade P-gp preventing drug resistance. It's very
exciting." P-gp, a protein first identified in 1976, sits in the membrane that
surrounds human cells, including those in the gut, intestine, kidney, and brain, where it
functions as a gate keeper, shooing out potentially harmful agents. Problematically, P-gp
not only transports substances that are harmful out of the cell, but also drugs targeted
to cancer cells and HIV-infected cells, as well as some therapeutics aimed at alleviating
psychiatric conditions. "We've long known that P-glycoprotein plays a key role in
multidrug resistance in cancer patients, and this work helps us understand how the protein
can act on such a wide range of compounds," said Jean Chin, Ph.D., of the National
Institutes of Health's (NIH) National Institute of General Medical Sciences (NIGMS), which
partially supported the work. "In the future, scientists may be able to use these
crystal structures to design chemicals that block P-glycoprotein's activity and restore
sensitivity to chemotherapeutic agents."
MBL researchers discover a
mechanism of neurodegeneration in Alzheimer's disease
Tiny, toxic protein particles severely
disrupt neurotransmission and inhibit delivery of key proteins in Alzheimer's disease, two
separate studies by Marine Biological Laboratory (MBL) researchers have found.
The particles are minute clumps of amyloid beta, which has long been known to accumulate
and form plaques in the brain of Alzheimer's patients. "These small particles that
haven't aggregated into plaques—these are increasingly being seen as the really toxic
species of amyloid beta," says Scott Brady of University of Illinois College of
Medicine, who has been an MBL investigator since 1982. Brady and his colleagues found that
these particles inhibit neurons from communicating with each other and with other target
cells in the body. "The disease symptoms for Alzheimer's are associated not with the
death of the neurons – that is a very late event – but with the loss of
functional connections. It's when the neuron is no longer talking to its targets that you
start to get the memory deficits and dementia associated with the disease," Brady
says.
The amyloid beta particles activate an enzyme, CK2, which in turn disrupts the "fast
axonal transport" system inside the neuron, Brady found. This transport system has
motor proteins that move various kinds of cargo (including neurotransmitters and the
associated protein machinery for their release) from place to place in the neuron on
microtubule tracks. Brady's findings are complemented by a new study by Rudolfo Llinás of
New York University School of Medicine. Brady and Llinás both conduct neuroscience
research at the MBL using the giant nerve cell of the Woods Hole squid, Loligo paeleii, as
a model system.
Concern over inappropriate
diagnosis and treatment of thyroid problems
More and more people are being
inappropriately diagnosed and treated for underactivity of the thyroid gland (known as
primary hypothyroidism), warn doctors in an editorial published on bmj.com today.
Hypothyroidism is caused by insufficient production of thyroid hormone by the thyroid
gland. It affects about three per cent of the population and is usually treated in primary
care. Blood tests are essential in confirming the diagnosis of hypothyroidism. But doctors
at the British Thyroid Association are concerned that, in recent years, increasing numbers
of patients with and without confirmed thyroid disease have been diagnosed and treated
inappropriately with thyroid hormones. "This is potentially an enormous problem,
given that in any one year one in four people in the United Kingdom have their thyroid
function checked," they warn. The Royal College of Physicians recently set out clear
guidance for the diagnosis and treatment of primary hypothyroidism in the United Kingdom,
so why have these problems arisen, ask the authors?
Hypothyroidism is common and is becoming more prevalent because of increased life
expectancy and an ageing population, they explain. Thyroid hormones also affect most
organs, so hypothyroidism presents with symptoms that can mimic other conditions. This can
lead to an incorrect diagnosis which could expose some patients to the harmful effects of
excess thyroid hormones, while other serious conditions may go undiagnosed. Information
available on the internet and media interest in alternative modes of diagnosis and
treatment of hypothyroidism, have also caused an increase in requests for inappropriate
investigations and non-standard treatments, as well as referrals to non-accredited
practitioners, they add.
Drinking very hot tea can increase
the risk of throat cancer
People are advised to wait a few minutes
before drinking a cup of freshly-boiled tea today as a new study, published on bmj.com,
finds that drinking very hot tea (70°C or more) can increase the risk of cancer of the
oesophagus, the muscular tube that carries food from the throat to the stomach. The study
was carried out in northern Iran, where large amounts of hot tea are drunk every day. But
an accompanying editorial says these findings are not cause for alarm and the general
advice is to allow foods and beverages to cool a little before swallowing. Cancers of the
oesophagus kill more than 500,000 people worldwide each year and oesophageal squamous cell
carcinoma (OSCC) is the commonest type. In Europe and America, it is mainly caused by
tobacco and alcohol use and is more common in men than in women, but drinking hot
beverages is also thought to be a risk factor. Golestan Province in northern Iran has one
of the highest rates of OSCC in the world, but rates of smoking and alcohol consumption
are low and women are as likely to have a diagnosis as men. Tea drinking, however, is
widespread, so researchers set out to investigate a possible link between tea drinking
habits and risk of OSCC. They studied tea drinking habits among 300 people diagnosed with
OSCC and a matched group of 571 healthy controls from the same area. Nearly all
participants drank black tea regularly, with an average volume consumed of over one litre
a day. Compared with drinking warm or lukewarm tea (65°C or less), drinking hot tea
(65-69°C) was associated with twice the risk of oesophageal cancer, and drinking very hot
tea (70°C or more) was associated with eight-fold increased risk.
Pregnant women who smoke, urged to
give up before 15-week 'deadline'
Women who stop smoking before week 15 of
pregnancy cut their risk of spontaneous premature birth and having small babies to the
same as non-smokers, according to research published on bmj.com today.
Women who do not quit by 15 weeks, are three times more likely to give birth prematurely
and twice as likely to have small babies compared to women who have stopped smoking, say
the researchers. The lead author, Dr Lesley McCowan at the University of Auckland, says
that maternity care providers need to emphasise to women the major benefits of giving up
smoking before 15 weeks in pregnancy with the goal of becoming smoke free as early in
pregnancy as possible. While it is well established that smoking in pregnancy increases
the risk of miscarriage, ectopic pregnancy, premature birth, small babies, stillbirth and
neonatal death, say the authors, no study has yet determined whether stopping smoking in
early pregnancy reduces the risks of small babies and premature births. The authors
surveyed over 2,500 pregnant women participating in the SCOPE study in Australia and New
Zealand at 15 weeks gestation. The participants were divided into three groups: non
smoker, stopped smoker and current smoker. The 'stopped smoker' group all gave up before
15 weeks of pregnancy.The results show that there were no differences between the rates of
premature birth between stopped smokers and non-smokers, whereas current smokers had much
higher risk. Similar results were revealed for expected baby size. Another important
finding was that women who stopped smoking were not more stressed than women who continued
to smoke.
Difference in fat storage may
explain lower rate of liver disease in African-Americans
Where different ethnic groups store fat in
their bodies may account for differences in the likelihood they'll develop insulin
resistance and non-alcoholic fatty liver disease, researchers at UT Southwestern Medical
Center have found. According to research reported in the online edition and the March
issue of Hepatology, African-Americans with insulin resistance might harbor factors that
protect them from this form of metabolic liver disease. Despite similarly high rates of
associated risk factors such as insulin resistance, obesity and diabetes among
African-Americans and Hispanics, African-Americans are less likely than Hispanics to
develop non-alcoholic fatty liver disease, or NAFLD. The disease is characterized by high
levels of triglycerides in the liver and affects as many as one-third of American adults.
"If we can identify the factors that protect African-Americans from this liver
disease, we may be able to extrapolate those to other populations and perhaps develop
targeted therapies to help populations prone to NAFLD," said Dr. Jeffrey Browning,
assistant professor of internal medicine in the UT Southwestern Advanced Imaging Research
Center and the study's senior author. Previous research has shown that when
African-Americans do develop NAFLD, they're less likely to reach the later stages of liver
disease. Prior work by Dr. Browning and other UT Southwestern scientists has revealed that
NAFLD is more prevalent among Hispanics than African-Americans or Caucasians. For the
current study, Dr. Browning and his colleagues analyzed data gathered in the multi-ethnic,
population-based Dallas Heart Study. Starting in the year 2000, more than 2,100
participants provided blood samples and underwent multiple body scans with magnetic
resonance imaging and computed tomography to examine the liver, heart and other organs.
Body composition, including fat distribution, also was scrutinized. The study found that
African-Americans and Hispanics both have obesity rates of about 48 percent among their
respective populations, as well as diabetes rates of about 21 percent. Only 23 percent of
African-Americans, however, have NAFLD, compared with 45 percent of Hispanics. Similarly,
African-Americans are less likely to have high levels of triglycerides and abdominal fat
– both characteristics of insulin resistance – when compared with Hispanics or
Caucasians, even though overall rates of insulin resistance among all groups are the same,
researchers found.
Targeting oxidized cysteine through
diet could reduce inflammation and lower disease risk
A team of scientists at Emory University
School of Medicine has identified a direct link between oxidative stress and inflammatory
signals in the blood. The finding could lead to improved strategies for preventing several
diseases by including antioxidants in the diet and for reducing the impact of inflammation
in critically ill patients by adding cysteine to intravenous or tube feeding. Many normal
metabolic functions produce reactive forms of oxygen that can damage cells. Oxidative
stress, a disruption of the body's ability to control reactive forms of oxygen, has been
connected with heart disease, diabetes and several neurodegenerative diseases. However,
scientists are still learning about the best ways to measure and reduce oxidative stress,
says Dean P. Jones, PhD, professor of medicine and director of the Clinical Biomarkers
Laboratory at Emory University School of Medicine. For example, large-scale clinical
trials have shown little benefit in supplementing the diet with antioxidants such as
vitamins C and E.Jones and his colleagues, including Thomas R. Ziegler, MD of the Emory
Department of Medicine, have been concentrating on a measure of oxidative stress in the
blood: cysteine, an amino acid found in most proteins in the body. Cysteine can exist in
two forms: oxidized and reduced. The higher the level of oxidative stress outside the
cell, the more oxidized cysteine there is. Other indicators such as glutathione are more
important inside cells. Several studies have shown that levels of oxidized cysteine in the
blood tend to rise as people age. Smoking and alcohol consumption are also linked with
higher levels of oxidized cysteine. In addition, Jones and Ziegler have found that
critical illness and malnutrition are associated with oxidative stress and oxidized
cysteine in the blood. Working with Jones, graduate student Smita Iyer and immunologist
Mauricio Rojas, MD, found that a high level of oxidized cysteine drives white blood cells
to send out inflammatory messages in the form of the protein IL-1 beta.
