- - European weblog on food, health and environment
News - Week 44 - 2008
A high-fat diet could promote the
development of Alzheimer's
A team of Université Laval researchers has shown that the main neurological markers
for Alzheimer's disease are exacerbated in the brains of mice fed a diet rich in animal
fat and poor in omega-3s. Details of the study—which suggests that diets typical of
most industrialized countries promote the development of Alzheimer's—are outlined in
the latest online edition of Neurobiology of Aging. To demonstrate this, the team led by
Frédéric Calon used a type of transgenic mice that produce two proteins found in the
brains of Alzheimer patients—tau proteins, which prevent proper neuron functioning,
and amyloid-beta, associated with the formation of senile plaques within the brains of
afflicted patients. The researchers fed transgenic and regular mice different diets
for nine months, after which they compared the effects on the animals' brains. The mice
whose diet was poor in omega-3s and rich in fat (60% of consumed calories) showed
amyloid-beta and tau protein concentrations respectively 8.7 and 1.5 times higher than the
control group mice, whose food contained 7 times less fat. The high-fat diet also reduced
drebrin protein levels in the brain, another characteristic of Alzheimer's disease.
"Metabolic changes induced by such a diet could affect the inflammatory response in
the brain," suggests study co-author Carl Julien to explain the link between fat
consumption and Alzheimer's. In most Western countries, diets rich in saturated fats and
poor in omega-3s are the norm. "Our findings lead us to believe that a diet
containing more omega-3s and less saturated fat could prevent the development of
Alzheimer's, at the very least among people genetically predisposed to the disease,"
comments Dr. Calon. "We cannot state with any certainty that what we have observed
among transgenic mice also occurs in humans, but there is no harm in eating less fat and
more omega-3s," concludes the researcher.
Recent studies hint that exposure to the toxic chemicals, such as methylmercury can
cause harm at levels previously considered safe. A new analysis of the epidemiological
evidence in the International Journal of Environment and Health, suggests that we should
take a precautionary approach to this and similar compounds to protect unborn children
from irreversible brain damage. Philippe Grandjean of the Department of
Environmental Health at Harvard School of Public Health, in Boston, and the University of
Southern Denmark in Odense, explains that the causes of suboptimal and abnormal mental
development are mostly unknown. However, severe exposure to pollutants during the
development of the growing fetus can cause problems that become apparent as brain
functions develop - and ultimately decline - in later life. Critically, much smaller doses
of chemicals, such as the neurotoxic compound methylmercury, can harm the developing brain
to a much greater extent than the adult brain. Methylmercury is a chemical compound formed
in the environment from released mercury. Unfortunately, the methylmercury can be
transported quickly around the body and may enter the brain. Serious problems will ensue
if important developmental processes are blocked as there will be only one chance for the
brain to develop. The researchers point out that until recently research into the effects
of pollutants on the brain has been clouded by the lack of information on actual exposure.
Moreover, finding a direct link between specific problems with the brain and exposure
relies on statistical, or epidemiological, analysis rather than case-by-case
understanding. The researchers say that neurodevelopmental disorders of possible
environmental origin affect between 5% and 10% of babies born worldwide, leading to
dyslexia, mental retardation, attention deficit/hyperactivity disorder, cerebral palsy,
and autism. The toxicity of methylmercury is well known, but the researchers believe that
the medical world has underestimated the risk of brain damage associated with exposure to
this compound as well as numerous others. Professor Grandjean emphasizes that little
research has been carried out into the effects of other neurotoxic chemicals. "Until
there is enough evidence to rule out effects of certain chemicals on the developing
nervous system, a cautious approach would involve strict regulation of suspected
developmental neurotoxicants and prudent counseling of expectant mothers regarding
exposures to untested substances," the researchers conclude.
A novel cell division mechanism has been discovered in a microorganism that thrives in
hot acid. The finding may also result in insights into key processes in human cells, and
in a better understanding of the main evolutionary lineages of life on Earth. The study is
published today in the online version the American National Academy of Sciences,
PNAS. The research group at the Department of Molecular Evolution at Uppsala
University has identified a completely cell division machinery. The discovery was made in
Sulfolobus acidocaldarius, a microorganism belonging to the third domain of life, the
Archaea, which originally was isolated from a hot spring in Yellowstone national park in
Wyoming, USA. Because of the extreme conditions, in which the cells grow optimally in acid
at 80ºC, the organism is of interest for a wide range of issues. They represent exciting
model systems in theories for how life once may have originated in hot environments on
early Earth, as well as in the search for life in extreme environments on other planets,
Professor Rolf Bernander explains. He is the scientist behind the study, together with
colleagues Ann-Christin Lindås, Erik Karlsson, Maria Lindgren and Thijs Ettema. The
researchers have identified three genes that are activated just prior to cell division.
The protein products from these genes form a sharp band in the middle of the cell, between
newly segregated chromosomes, and then gradually constrict the cell such that two new
daughter cells are formed.
A groundbreaking study by two University of Rochester psychologists to be published
online Oct. 28 by the Journal of Personality and Social Psychology adds
color—literally and figuratively—to the age-old question of what attracts men to
women. Through five psychological experiments, Andrew Elliot, professor of psychology, and
Daniela Niesta, post-doctoral researcher, demonstrate that the color red makes men feel
more amorous toward women. And men are unaware of the role the color plays in their
attraction. The research provides the first empirical support for society's enduring love
affair with red. From the red ochre used in ancient rituals to today's red-light districts
and red hearts on Valentine's Day, the rosy hue has been tied to carnal passions and
romantic love across cultures and millennia. But this study, said Elliot, is the only work
to scientifically document the effects of color on behavior in the context of
relationships.
Scientists identify cell changes
leading to impaired 'artificial kidney' function
Molecular targets identified by a Spanish research team may hold the key to freedom for
some sufferers of kidney disease. A new study published in Disease Models & Mechanisms
(DMM), dmm.biologists.org, reveals the cellular signals which cause one treatment for
kidney failure to lose its usefulness over time. One of the most devastating aspects of
kidney failure is the strict, time-consuming treatment regimen. Normally, healthy kidneys
take on the role of filtering and cleaning the blood. Therefore patients with diseased
kidneys traditionally need to attend a dialysis clinic to have their blood cleaned through
a special filter. This treatment requires three regular clinic visits per week, with each
session lasting three to five hours. An alternative to this treatment involves creation of
an "artificial kidney" in a process known as peritoneal dialysis (PD). Fluid is
inserted into the abdominal cavity, and the blood vessel-rich cavity lining, the
peritoneum, acts as a filter for the blood. Exchanges of dialysis fluid can take place at
home, thus freeing patients of a rigid schedule of clinic visits.
Temple researchers look for
behavioral link between breastfeeding and lower risk of obesity
Breastfeeding has a number of positive health benefits for baby: it can prevent ear
infections and allergies, and lowers the risk of developing respiratory problems. It can
also help prevent against obesity later in life, but the reason for this still isn't
known. In an effort to find this link, Katherine F. Isselmann, M.P.H., a doctoral
candidate in Temple's department of public health, has been comparing the feeding habits
of mothers who breastfed their babies and mothers who bottle fed their babies, and has
also examined the eating habits of their pre-school aged children. In preliminary research
presented at this year's American Public Health Association annual meeting on Oct. 28,
Isselmann and faculty members in the department of public health at the College of Health
Professions surveyed more than 120 mothers on whether they had breastfed or bottle-fed
their babies, using either pumped breast milk or formula. They found breastfed children
could more easily determine when they were full. Children who were bottle-fed with pumped
breast milk were less likely to respond to the feeling of being full by the time they were
preschool-aged. Also, children who had a lower response to fullness had a higher body mass
index (BMI). According to Isselmann, these results suggest a behavioral link between
breastfeeding and obesity prevention, in that children who are breastfed grow to have more
positive eating behaviors, which could help prevent obesity later in life.
New research presented at CHEST 2008 shows that patients treated for their prolonged
seizures with the sedative propofol may be at high risk for complications and even death.
New research presented at CHEST 2008 found that patients who received transfusions with
blood stored for 29 days or more were twice as likely to suffer from nosocomial
infections, including pneumonia, upper respiratory infections and sepsis, with the oldest
blood being associated with the most infections. Currently, federal regulations allow red
blood cells to be stored up to 42 days, after which they must be discarded.
New research presented at CHEST 2008 shows that nicotine dependence has reached a
15-year high, with nearly 75 percent of people currently seeking tobacco-dependence
treatment categorized as highly nicotine dependent.
New understanding of how we
remember traumatic events
Neuroscientists at The University of Queensland have discovered a new way to explain
how emotional events can sometimes lead to disturbing long term memories. In evolutionary
terms, the brain's ability to remember a fear or trauma response has been crucial to our
long term survival. However, in the modern world, when a similar type of fear response is
triggered by a traumatic event such as being in combat; being exposed to abuse or being
involved a major car accident, we do not want to repeatedly re-experience the episode, in
vivid detail, for the rest of our lives. During studies of the almond-shaped part of the
brain called the amygdala – a region associated with processing emotions –
Queensland Brain Institute (QBI) scientists have uncovered a cellular mechanism underlying
the formation of emotional memories, which occurs in the presence of a well known stress
hormone. In a scientific paper published in the Journal of Neuroscience, QBI's Dr Louise
Faber and her colleagues have demonstrated how noradrenaline, the brain's equivalent of
adrenaline, affects the amygdala by controlling chemical and electrical pathways in the
brain responsible for memory formation. "This is a new way of understanding how
neurons form long term memories in the amygdala," Dr Faber said.
How toxic environmental chemical
DBT affects the immune system
An international team of researchers at the University of California, San Diego School
of Medicine and the University of Basel in Switzerland have issued a report on the
mechanism of toxicity of a chemical compound called Dibutyltin (DBT). Their findings will
be published by PLoS ONE on October 28. DBT is part of a class of high toxic and
widely distributed chemical compounds called organotins, DBT is most commonly used as an
anti-fouling agent in paint, for example in the fishing and shipbuilding industries. It is
also used in the production of polyvinyl chloride (PVC) plastic tubes and bottles.
According to co-lead investigators Michael E. Baker, Ph.D., researcher in UC San Diego's
Department of Medicine, Division of Nephrology-Hypertension, and Alex Odermatt, Ph.D., at
the University of Basel, DBT is closely related to tributyltin (TBT), another well-known
pollutant. Concern about the side effects of TBT led the United Nations' International
Maritime Organization to organize a global ban on its use. "TBT is metabolized by the
body's liver into DBT," the scientists explained. "Humans are also exposed to
DBT by drinking water from PVC pipes. Because it is poorly broken down, DBT remains in the
environment and it appears that its toxic effects are more rapid and more pronounced than
those of TBT." Symptoms of organotin exposure can include irritated skin, dizziness,
difficulty breathing, and flu-like symptoms. Although long-terms effects in humans are
uncertain, large doses of certain organotins have been shown to damage the reproductive
and central nervous systems, bone structure, the liver and immune system in mammals.
New hormone data can predict
menopause within a year
For many women, including the growing number who choose later-in-life pregnancy,
predicting their biological clock's relation to the timing of their menopause and
infertility is critically important. Now, investigators from the University of Michigan
have provided new information about hormonal biomarkers that can address the beginning of
the menopause transition. "In the end, this information can change the way we do
business," said MaryFran Sowers, professor in the U-M School of Public Health
Department of Epidemiology. "The information provides a roadmap as to how fast women
are progressing through the different elements of their reproductive life."
Researchers at UH Explore use of
Fat Cells as Heart Attack Therapy
For those of us trained to read nutrition labels, conventional wisdom tells us that fat
isn’t good for the heart. But a team of University of Houston researchers has set out
to use fat cells to beef up heart muscles damaged by heart attack – and it's using an
out-of-this-world device to do it. While associate professor Stanley Kleis and his
research team at the Cullen College of Engineering’s department of mechanical
engineering aren’t advocating a fried-food free-for-all, they do see the promise of
using adipose-derived stromal cells (ADSCs), which are found in fatty tissue, as a therapy
for heart attack patients. When a patient has a heart attack, the heart cells do not get
enough oxygen-rich blood, and some of them die, leaving behind damaged tissue. The ADSCs
are a bit like stem cells, because they have the potential to develop into different types
of cells, and they can produce chemicals that may protect or rejuvenate heart muscles.
“If we can show this conclusively, then we can develop a procedure that doctors can
use to inject the cells into a heart attack patient’s heart and can either protect or
even help regrow the heart muscles,” Kleis said.
Large hormone dose may reduce risk
of post-traumatic stress disorder
A new study by Ben-Gurion University of the Negev (BGU) researchers found that a high
dose of cortisone could help reduce the risk of post-traumatic stress disorder (PTSD). The
article appears in Biological Psychiatry, Volume 64, Issue 8 (October 15, 2008), pages
708-717. In an animal model of PTSD, high doses of a cortisol-related substance,
corticosterone, prevented negative consequences of stress exposure, including increased
startle response and behavioral freezing when exposed to reminders of the stress. Cortisol
is secreted into the blood stream through the adrenal glands, which are active when the
body responds to stress. It is known as "the stress hormone" because it is also
secreted in higher levels during the body's "fight or flight" response to
stress, and is responsible for several stress-related changes in the body.
In the first study ever to genetically link the immune system to normal behavior,
scientists at Rockefeller and Columbia universities show that mast cells, known as the
pharmacologic bombshells of the immune system, directly influence how mice respond to
stressful situations. The work, to appear this week in the Proceedings of the National
Academy of Sciences and to be highlighted in Science, chips away at the increasingly stale
idea that the two most complex systems in the body have entirely separate modes of
operation. Eight years ago, scientists from Columbia University discovered that mast cells
travel to the brain from other organs early on in development. "We now knew that mast
cells resided in the brain but we didn't know their function," says Rockefeller
University's Donald Pfaff, head of the Laboratory of Neurobiology and Behavior. "But
we know that they synthesize a large number of important chemical mediators that could
potentially have severe neurophysiological effects." Since then, mast cells have been
associated with several behaviors and conditions. For example, the number of mast cells
and anxiety levels in mice have been shown to ebb and flow with the onset of stressful
conditions, including asthma and food allergies. Lethargy has also been associated with an
excess of mast cells. "However, we have now been the first to manipulate mast cells
genetically and pharmacologically and show an immediate behavioral effect," says
Pfaff.
Pregnant women consuming flaxseed
oil have high risk of premature birth
The risks of a premature birth quadruple if flaxseed oil is consumed in the last two
trimesters of pregnancy, according to a new study from the Université de Montréal and
the Sainte-Justine Hospital Research Center.
Scientists identify new gene
responsible for puberty disorders
A new gene responsible for some puberty disorders has been identified by Medical
College of Georgia researchers. They found that the gene mutated in CHARGE syndrome –
a multi-system disorder characterized by diverse problems from heart defects to hearing
loss to cleft lip and palate and mental retardation – also accounts for about 6
percent of two puberty disorders. These disorders – idiopathic hypogonadotropic
hypogonadism, or IHH, and Kallmann syndrome – short circuit puberty and can cause
infertility. Kallmann syndrome is also marked by patients’ inability to smell.
Dr. Lawrence Layman, chief of the MCG Section of Reproductive Endocrinology, Infertility
and Genetics in the School of Medicine, and colleagues published an article in the October
issue of The American Journal of Human Genetics linking the diseases.
Researchers at Rhode Island Hospital have created the first animal model that can
reveal the side effects of anesthetic agents (the substances used to block pain during
surgery) in individuals genetically predisposed to sudden cardiac death. The researchers
also found that some anesthetic agents may trigger arrhythmias. The study appears in an
upcoming issue of the American Journal of Physiology – Heart Circulation Physiology
and is currently available online. Researchers know that genetic mutations can predispose
individuals to arrhythmia and/or sudden cardiac death (SCD), a leading cause of death in
the United States. Between one in 2,500 and one in 5,000 individuals are born with
mutations that cause long QT syndrome (LQTS), a disorder of the heart's electric system,
and a determining factor in the development of arrhythmia and/or SCD. Ninety percent of
the known mutations cause loss of function of ion channels responsible for LQTS types 1
and 2 (LQT1 and LQT2). LQTS leads to a prolonged QT interval on electrocardiograms. The QT
interval refers to the time it takes the chambers of the heart to "repolarize"
themselves so that the heart is ready for another contraction cycle. When this timeframe
is lengthened, it is associated with triggering irregular arrhythmia that can cause sudden
cardiac arrest. Earlier this year, researchers at the Cardiovascular Research Center at
Rhode Island Hospital developed a first-of-its-kind genetic animal model to study
arrhythmia and SCD that mirrors what happens in individuals who have mutations of the LQT1
or LQT2 genes. With the rising interest in pharmacogenomics (the study of the effect of an
individual's genotype on the body's potential response to medications) the researchers
have taken the model one step further and have developed what they believe is the first
model to test the safety and efficacy of drugs such as anesthetics when these genetic
mutations are present.
Stress during pregnancy has
detrimental effect on offspring
That stress during a mother's pregnancy can cause developmental and emotional problems
for offspring has long been observed by behavioral and biological researchers, but the
objective measuring and timing of that stress and its results are difficult to prove
objectively in humans. However, Prof. Marta Weinstock-Rosin of the Hebrew University of
Jerusalem School of Pharmacy, in her experimental work with rats, has been able to
demonstrate that relationship in a conclusive, laboratory-tested manner.
Scripps research scientists develop
a new strategy to fight obesity
The antibody works against the gastric hormone ghrelin (pronounced
"grell-in"), which has been linked to weight gain and fat storage through its
metabolic actions. These findings point towards a potentially novel treatment for obesity
that would interfere directly with the some of the biological mechanisms determining
weight. The study is being published the week of October 27, 2008, in an advance, online
Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS). In
the study, which was led by investigators Kim Janda and Eric P. Zorrilla of The Scripps
Research, the antibody catalyst GHR-11E11 led to a higher metabolic rate in fasting mice
and suppressed feeding following 24-hour food deprivation. "Our study showed that
this novel catalytic ghrelin antibody could specifically seek out and degrade
ghrelin," said Janda, who is Ely R. Callaway, Jr. Professor of Chemistry, member of
The Skaggs Institute for Chemical Biology, and director, Worm Institute of Research and
Medicine (WIRM), at Scripps Research. "While this antibody lacks a high level of
catalytic efficiency, our study clearly demonstrates that even a basal level of catalysis
can effectively modulate feeding behavior. These findings not only validate antibody-based
therapeutics, but strongly suggest that catalytic anti-ghrelin antibodies might help
patients reach and maintain their weight loss goals." According to recent reports
from the World Health Organization, about 1 billion people worldwide are overweight or
obese, with most of these in the developed world. In the United States, for example, the
National Health and Nutrition Examination Survey found that, in 2003-2004, approximately
66 percent of all adults 20 years of age or older were overweight or obese. Almost four
out of every five American men aged 40 to 59 were classified as overweight, according to a
2006 study published by the Journal of the American Medical Association. While
non-surgical treatments can be modestly effective against obesity, weight loss or gain can
be affected by ghrelin, which is released by the body to encourage eating during periods
of calorie restriction. A gastric endocrine hormone produced primarily in the stomach,
ghrelin promotes weight gain and fat storage through its metabolic actions, decreasing the
break down of stored fat for energy as well as energy expenditure itself.
Restrictions on Off-Label Marketing
and Promotion of Drugs by Pharmaceutical Companies Should be Strengthened, Researchers Say
Researchers are asking for tougher penalties and fines for pharmaceutical companies
that market drugs for “off label” promotion, according to a study published in
the October 28 issue of the open access journal PLoS Medicine. New regulations are needed
to address this practice, say Adriane Fugh-Berman, M.D., an associate professor in the
GUMC Department of Physiology and Biophysics, and Douglas Melnick, M.D., a preventive
medicine physician in the Los Angeles County Department of Public Health. In the article,
Fugh-Berman and Melnick address public health issues associated with off-label promotion
and marketing.
Both authors have extensive experience with the pharmaceutical industry. Melnick once
worked in as a physician in industry medical affairs, which supported pharmaceutical
marketing efforts. Fugh-Berman is the principal investigator of PharmedOut, a
publicly-funded project to educate physicians about the influence that pharmaceutical
companies have on drug prescribing.
A lack of specific brain receptors has been linked with schizophrenia in new research
by scientists at Newcastle University. In work published today in the Proceedings of the
National Academy of Sciences, the team has found that NMDA receptors are essential in
modifying brain oscillations – electrical wave patterns – which are altered in
patients with schizophrenia. They now want to investigate whether optimising the function
of the receptors, which are already know to be involved in making memories, could lead to
a new way of treating the mental illness. Schizophrenia is one of the most common serious
mental health conditions in the UK and can cause a range of different psychological
symptoms, including hallucinations and delusions. One in 100 people will experience at
least one episode of acute schizophrenia during their lifetime and it affects men and
women equally. While its exact cause is unknown, most experts believe that the condition
is caused by a combination of genetic and environmental factors.
Current research suggests that stress may activate immune cells in your skin, resulting
in inflammatory skin disease. The related report by Joachim et al., "Stress-induced
Neurogenic Inflammation in Murine Skin Skews Dendritic Cells towards Maturation and
Migration: Key role of ICAM-1/LFA-1 interactions," appears in the November issue of
The American Journal of Pathology. Skin provides the first level of defense to infection,
serving not only as a physical barrier, but also as a site for white blood cells to attack
invading bacteria and viruses. The immune cells in skin can over-react, however, resulting
in inflammatory skin diseases such as atopic dermatitis and psoriasis. Stress can trigger
an outbreak in patients suffering from inflammatory skin conditions. This cross talk
between stress perception, which involves the brain, and the skin is mediated the through
the "brain-skin connection". Yet, little is know about the means by which stress
aggravates skin diseases.
Osteoporosis drugs increase risk
for heart problems
New research, presented at CHEST 2008 shows that people taking alendronate or
zoledronic acid, two common medications to prevent or slow the occurrence of osteoporosis,
were significantly more likely to experience serious atrial fibrillation, including
hospitalization or death, compared with placebo.
UI study may explain
exercise-induced fatigue in muscular dystrophies
A University of Iowa study suggests that the prolonged fatigue after mild exercise that
occurs in people with many forms of muscular dystrophy is distinct from the inherent
muscle weakness caused by the disease.
The research, which was published Oct. 26 in Nature Advance Online Publication, identifies
a faulty signaling pathway that appears to cause exercise-induced fatigue in mouse models
of muscular dystrophy. Moreover, the study shows that Viagra can overcome the signaling
defect and relieve the fatigue. The findings suggest that targeting the signaling pathway
may lead to therapies for this type of fatigue.
"This is an exciting finding and our research suggests that there probably are many
different neuromuscular conditions where fatigue could be treated by targeting this newly
discovered pathway," said Kevin Campbell, Ph.D., professor and head of molecular
physiology and biophysics at the UI Carver College of Medicine and a Howard Hughes Medical
Institute investigator, who holds the Roy J. Carver Chair of Physiology and Biophysics.
Using animal models, the researchers showed that if an enzyme called neuronal nitric oxide
synthase (nNOS) is not present at its normal location on the muscle membrane, then blood
vessels that supply active muscles do not relax normally, and the animals experience
post-exercise fatigue.
When Memorial Sloan-Kettering Cancer Center announces that vitamin C may interfere with
chemotherapy, the news media trumpet it far and wide. But before cancer patients throw
away their vitamin C supplements, they need to know rest of the story.
Vitamin D: as close to a magic
bullet as you can get?
In our view, many health authorities have got people far too frightened about the sun.
There are generations of kids growing up in parts of the US, Australia and other climes
where the sun shines more than it doesn't who are sun averse. They either cover themselves
with total block 30-50 SPF sunscreen, which itself may pose a risk to health, or even skin
cancer, or they hide away indoors playing computer games or watching television to escape
the sun's supposedly dangerous rays.
About half of American doctors in a new survey say they regularly give patients placebo
treatments — usually drugs or vitamins that won’t really help their condition.
And many of these doctors are not honest with their patients about what they are doing,
the survey found.
The dramatic video titled Smoking Teeth = Poison Gas has had a tremendous impact on
both the public and professional audiences.The full version plays 40 minutes with
interviews of experts in the fields of mercury toxicology, environmental medicine,
politics and dentistry.
Lorraine Day's battle of
cancer
Eye-opener of the fight against cancer by
an American doctor using all natural solutions.
Nitric oxide in inflammation and
pain associated with osteoarthritis
he role played by NO in the function of normal and pathological joints is still
incompletely understood. Although it is clear that NO and RNOS both play a role in the OA
disease process, as well as in the perception of pain, studies analyzing the effects of
NO-donating agents in both chondrocytes and other cell types are providing insights that
suggest that there are also protective functions for NO and its redox derivatives in
individual cell types. Future research into the role played by NO in OA and the utility of
NO-donating agents may provide a new therapeutic option for the treatment of OA with an
improved risk profile compared with currently available therapies.
David Servan-Schreiber Conference on Natural Methods f Healing from Depression. Place:
the American church of Paris.
Best of TED
Good thoughts, views, and ideas from great minds
Rheumatoid Arthritis Patients do
Worse After a Heart Attack
Following a heart attack, people with rheumatoid arthritis (RA) suffer greater
heart-related complications, including an increased risk for dying, when compared to other
heart attack patients, according to research presented this week at the American College
of Rheumatology Annual Scientific Meeting in San Francisco. Mayo Clinic researchers
determined that patients with RA do suffer higher mortality and are at higher risk of
heart failure after a heart attack, but reasons for the increase are still unknown. The
results of this study emphasize the need for better strategies for prevention, diagnosis
and treatment of heart attacks in these patients.
After four decades on the decline, rheumatoid arthritis is on the upswing among women in
the United States. That's the finding presented by Mayo Clinic investigators at the annual
meeting of the American College of Rheumatology/Association of Rheumatology Health
Professionals in San Francisco."This is a significant finding and an indicator that
more research needs to be done to better understand the causes and treatment of this
devastating disease," says Sherine Gabriel, M.D., Mayo Clinic rheumatologist and lead
investigator on the study.From 1955 to 1994, the incidence of rheumatoid arthritis had
continually been on the decline. That apparently changed beginning in the mid-1990s. When
Mayo researchers analyzed patient data from early 1995 to the start of 2005, they found
that both the incidence and prevalence (percentage) of the condition were rising.
A report from the American Academy of Pediatrics says children, from newborns to teens,
should get twice the previously recommended daily amount of Vitamin D. New studies have
found it may help reduce risks of cancer, diabetes and heart disease, in addition to
keeping bones strong. Those studies mean that many American children, like David Osorio,
are Vitamin D deficient, reports CBS News medical correspondent Dr. Jon LaPook. Osorio is
only six-years-old and has already suffered bone fractures in both arms.
A reversal of thinking - How women
with lupus can increase chance for healthy pregnancies.
In the not so distant past, women with systemic lupus erythematosus, an autoimmune
disease, were advised not to have children, and if they became pregnant, to have
therapeutic abortions to prevent severe flares of their lupus. Research by rheumatologists
at Hospital for Special Surgery in New York, in patients with lupus who have had
successful pregnancies is yielding insights that support a reversal of that thinking.
Researchers at the Heidelberg University Hospital discover new genetic disease / Gene
mutation that triggers severe cirrhosis of the liver identified / Published in
“Hepatology” Researchers at the Heidelberg University Hospital have discovered a
new genetic disease that can lead to severe liver damage. Because a protective component
of the bile is missing, the liver cells are exposed to the toxic components of the bile,
resulting in cirrhosis of liver, a transformation of liver cells into connective tissue
with a gradual loss of liver function. This could explain some of the cases of liver
cirrhosis of unknown origin and open up a new approach for treatment. The research has now
been published in the journal “Hepatology”.Some of the known frequent causes of
cirrhosis of the liver are liver inflammation due to a virus, alcohol abuse, autoimmune
disease, and metabolic defects. But in some 15 to 20 percent of patients, the cause is
unknown and the appropriate treatment cannot be initiated.
Even mild sleep apnea increases
cardiovascular risk
People with even minimally symptomatic obstructive sleep apnea (OSA) may be at increased
risk for cardiovascular disease because of impaired endothelial function and increased
arterial stiffness, according to a study from the Oxford Centre for Respiratory Medicine
in the UK. "It was previously known that people with OSA severe enough to affect
their daytime alertness and manifest in other ways are at increased risk of cardiovascular
disease, but this finding suggests that many more people—some of whom may be
completely unaware that they even have OSA—are at risk than previously thought,"
said lead author of the study, Malcolm Kohler, M.D. The study will be published in the
first issue for November of the American Thoracic Society's American Journal of
Respiratory and Critical Care Medicine. "Only one out of approximately five subjects
with [clinically defined OSA] complains of excessive daytime sleepiness in population
studies," wrote Geraldo Lorenzi-Filho, M.D., Ph.D. in an editorial in the same issue
of the Journal. "[I]t is now recognized that OSA triggers a cascade of biological
reactions, including increased sympathetic activity, systemic inflammation, oxidative
stress, and metabolic alterations that are potentially harmful to the cardiovascular
system." To determine the exact nature of some of these effects, Dr. Kohler and
colleagues performed a controlled, cross-sectional study to assess differences in
endothelial function (often a harbinger for cardiovascular problems to come), arterial
stiffness and blood pressure in patients with minimally symptomatic OSA. They compared 64
patients who had proven OSA to matched control subjects without OSA.
New Test Promises Quicker, More
Accurate Evaluation for Cystic Fibrosis Patients
Researchers at National Jewish Health have identified a simple gene-based blood test that
more accurately and quickly measures cystic fibrosis patients’ response to therapy
than current tests. The test, a measure of inflammatory gene expression, could improve
patient care and help clear a backlog of promising medications now hung up in clinical
trials. The researchers are publishing the results of a small
“proof-of-principal” trial in the November 1, 2008, issue of American Journal of
Respiratory and Critical Care Medicine . “The currently accepted test, a measure of a
patients’ ability to exhale air, has several limitations that make it ineffective for
some patients and not sensitive enough for clinical trials of many new medications,”
said Dr. Milene Saavedra, lead author of the study and Assistant Professor of Medicine at
National Jewish Health. “By measuring the activity of genes associated with the
immune/inflammatory response, we can get a more accurate picture of the biological
processes occurring inside the lungs.” Cystic fibrosis is the most common lethal
inherited disease in the western world, with about 30,000 patients in the US . Most
patients die of respiratory failure generally in their 30s or 40s. Lung damage is caused
primarily by chronic bacterial infections and the resulting severe airway inflammation.
There is a critical need for new effective anti-microbial and anti-inflammatory
medications to slow and/or prevent lung damage in young patients. Several promising
therapies have gone through early stages of clinical testing but their progress is being
hampered by the lack of a sensitive measure of therapeutic response to medications.
Speaking at the EG conference, "renegade lunch lady" Ann Cooper talks about
the coming revolution in the way kids eat at school -- local, sustainable, seasonal and
even educational food.
Light products and breast
cancer
Research shows potential health risks of
sugar substitutes, especially those containing Aspartame. Is diet soda causing cancer and
obesity? CBN News reports.
Allen Richardson worked on the White Earth Land Recovery Project’s wild rice
campaign, under the leadership of Native American activist and author Winona LaDuke. He
explains that when the Ojibwa, who consider wild rice to be their cultural property and a
gift from God, learned that researchers at the University of Minnesota planned to
genetically engineer wild rice, they opposed the project. As an advocate and lobbyist,
Richardson worked successfully toward passage of a state bill that prevents wild rice from
being genetically engineered.
Mechanism in cells that generate
malignant brain tumors may offer target for gene therapy
Researchers at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute who
first isolated cancer stem cells in adult brain tumors in 2004 have now identified a
molecular mechanism that is involved in the development of these cells from which
malignant brain tumors may originate. This could offer a target for scientists seeking
treatments that would kill malignant brain tumors at their source and prevent them from
recurring. Normal stem cells are "immature" cells that have the potential to
become any of several types of cells. Cancer stem cells have the same multi-potent and
self-renewing properties, but instead of producing healthy cells, they propagate cancer
cells. Theoretically, if these "mother cells" can be destroyed, the tumor will
not be able to sustain itself. On the other hand, if these cells are not removed or
destroyed, the tumor will continue to return despite the use of existing cancer-killing
therapies. Glioblastoma multiforme is the most malignant form of tumor that develops in
the brain, but not all glioblastomas are identical. Subgroups are comprised of cells
originating from different brain tumor stem cells with unique genetic characteristics that
use different signaling pathways in their development and growth. The Cedars-Sinai
researchers are building genetic "profiles" of these cancer stem cells and the
tumors they appear to produce. In this study, published in the journal Stem Cells (Stem
Cells Express online Sept 11., ahead of print), the researchers identified a subset of
brain tumor stem cells that is dependent on a protein called Sonic Hedgehog and another
subset that is not Hedgehog dependent. The brain tumors resulting from each subset
retained the "signaling dependency" characteristics of the mother cells, and in
laboratory experiments and studies in laboratory mice, pathway-specific blocking
interventions prevented the brain tumor stem cells from being able to renew themselves.
Making flies sick reveals new role
for growth factors in immunity
A Salmonella infection is not a positive experience. However, by infecting the common
laboratory fruit fly Drosophila melanogaster with a Salmonella strain known for causing
humans intestinal grief, researchers in the School of Life Sciences at Arizona State
University have shed light on some key cell regulatory processes – with broad
implications for understanding embryonic development, immune function and congenital
diseases in humans. Associate Professor Stuart Newfeld and laboratory coordinator Joel
Frandsen, along with colleagues in the College of Liberal Arts and Sciences and Biodesign
Institute at ASU, released their findings online on September 24 in the journal
Proceedings of the National Academy of Sciences. Strong parallels exist in the regulation
of immune system function in animals as diverse as flies, mice, and humans. Newfeld's own
investigative connection between fly and human immune systems came about through his
research with a well-studied family of proteins called Bone Morphogenetic Proteins (BMP).
"Bones and flies?" one might scoff. These proteins are named because of their
involvement in the formation of bone and cartilage in humans; however, they have also been
linked to many other aspects of early development and to essential cellular processes in
virtually all animals. One type of morphogenetic protein, intensively studied in fruit
flies and the focus of the published study by the Newfeld group, is the growth factor
Decapentaplegic (Dpp). Dpp acts as a hormonal signaling device, binding to cells and
communicating, for instance, whether to divide or to stop growing or even to become a
different type of cell. Studies have shown that Dpp in the fruit fly and its counterparts
in other animals have diverged little from one another in evolutionary time. Although
there are tiny changes in the genes that code for this protein from animal to animal, the
morphogenetic proteins are still structurally and functionally very similar – a
testament to their crucial role as signaling devices in all animals, including humans.
A powerful antioxidant in green tea may prevent or delay the onset of type 1 diabetes,
Medical College of Georgia researchers say.Researchers were testing EGCG, green tea's
predominant antioxidant, in a laboratory mouse with type 1 diabetes and primary Sjogren's
syndrome, which damages moisture-producing glands, causing dry mouth and eyes. "Our
study focused on Sjogren's syndrome, so learning that EGCG also can prevent and delay
insulin-dependent type 1 diabetes was a big surprise," says Dr. Stephen Hsu,
molecular/cell biologist in the School of Dentistry.
There is a cancer in the United States that isn’t sneaking up on us; it’s
already here. Cancer of the esophagus is one of just two cancers that are increasing in
this country (skin cancer is the second) and the western world. In fact, figures from the
National Cancer Institute show cancer of the esophagus has gone up 400 percent since 1975.
And as the cancer spreads, its sufferers aren’t who they used to be. “Thirty
years ago, nearly all of the cancer of the esophagus was occurring in African Americans
and people who smoke and drank excessively, since alcohol and tobacco cause cancer,”
says Joel Richter, M.D., chair of the Department of Medicine at Temple University School
of Medicine and Richard L. Evans Professor of Medicine. “Now, it’s more common
in Caucasians, and it’s related to the gastro-esophageal reflux disease, or GERD,
epidemic.” The rise of gastro-esophageal reflux is caused by two factors, one of
which is tied right to our gut. The obesity epidemic sweeping America is the culprit
behind many health issues and extra weight can cause GERD. A second factor is the
reduction of the H. pylori bacteria. Though you might think that getting rid of a nasty
bug that causes digestive troubles, stomach ulcers and stomach cancer would be a good
thing, eradicating H. pylori through antibiotics has created a “catch-22” in our
stomachs.
Spirituality protects against
depression better than church attendance
Those who worship a higher power often do so in different ways. Whether they are active in
their religious community, or prefer to simply pray or meditate, new research out of
Temple University suggests that a person's religiousness – also called religiosity
– can offer insight into their risk for depression. Lead researcher Joanna Maselko,
Sc.D., characterized the religiosity of 918 study participants in terms of three domains
of religiosity: religious service attendance, which refers to being involved with a
church; religious well-being, which refers to the quality of a person's relationship with
a higher power; and existential well-being, which refers to a person's sense of meaning
and their purpose in life.In a study published on-line this month in Psychological
Medicine, Maselko and fellow researchers compared each domain of religiosity to their risk
of depression, and were surprised to find that the group with higher levels of religious
well-being were 1.5 times more likely to have had depression than those with lower levels
of religious well-being. Maselko theorizes this is because people with depression tend to
use religion as a coping mechanism. As a result, they're more closely relating to God and
praying more.
Major Source of Radon Exposure
Overlooked at Former Ohio Uranium Processing Plant
University of Cincinnati (UC) scientists say that a recent scientific study of a
now-closed uranium processing plant near Cincinnati has identified a second, potentially
more significant source of radon exposure for former workers. That source—six silos
filled with uranium ore in the production area—resulted in relatively high levels of
radon exposure to 12 percent of the workers. More than half (56 percent) of the workers
were exposed to low levels of radon while working at the site. “Our findings have
scientific and political ramifications,” explains Susan Pinney, PhD, corresponding
author of the study and associate professor of environmental health at UC. “Now we
know workers in the plant’s production area prior to 1959 may be at increased risk
for developing lung cancer and other exposure-related health problems.” Third-shift
plant workers were most affected, during some years being exposed to three times more
harmful radon gas than workers on other shifts, according to the UC study. Researchers say
the elevated exposure was the result of decreased air movement and less dispersion of
radon gas during the night.
Research uncovers new steps on
pathway to enlarged heart
Researchers have new insight into the mechanisms that underlie a pathological increase in
the size of the heart. The research, published by Cell Press in the October 24th issue of
the journal Molecular Cell, may lead to the development of new strategies for managing
this extremely common cardiac ailment that often leads to heart failure. High blood
pressure, heart valve disease and heart attacks can lead to a abnormal thickening of the
heart muscle, called myocardial hypertrophy. At the molecular level, signals driving
myocardial hypertrophy, such as elevated levels of catecholamine hormones (i.e.
adrenaline), activate the Myocyte Enhancer Factor (MEF) proteins. This alters gene
expression in heart muscle cells and induces an adverse developmental paradigm known to
cardiologists as the "fetal gene response". "Previous research has shown
that the signaling pathways leading to MEF2 are altered during pathological cardiac
hypertrophy," says senior study author Dr. John D. Scott, a Howard Hughes Medical
Institute Investigator from the Department of Pharmacology at the University of
Washington. "Although we know that enzymes called histone deacetylases (HDACs)
control MEF2 activity, it was not clear that HDACs and MEF2 were integrated into a larger
signaling unit." To further identify the molecular mechanisms associated with cardiac
hypertrophy, Dr. Scott and colleagues studied cardiac A-Kinase Anchoring Proteins (AKAPs),
which are known to play a critical role in organizing signaling complexes in response to
catecholamine hormones and transmitted signals within cells.
Elderly Women Can Increase Strength
But Still Risk Falls
Elderly women can increase muscle strength as much as young women can, a new study from
the University of New Hampshire finds, indicating that decline in muscle function is less
a natural part of the aging process than due to a decline in physical activity. The
research, published in the journal Medicine & Science in Sports & Exercise,
compared strength gains of inactive elderly women and inactive young women after both
groups participated in an eight-week training regime. Yet while the two groups increased
similar percentages of strength, the older group was far less effective in increasing
power, which is more closely related to preventing falls. "Power is more important
than strength for recovery from loss of balance or walking ability," says Dain
LaRoche, assistant professor of exercise science at UNH and the lead author of the study.
Preventing falls, which occur in 40 percent of people over 65 and are the top reason for
injury-related emergency room visits, is the driving force behind LaRoche's research
agenda. LaRoche compared the initial strength of 25 young (18 - 33) and 24 old (65 - 84)
inactive women then had both groups participate in resistance training on a machine that
targeted knee extensor muscles, which are critical for walking, stair-climbing, or rising
from a chair. "They're what let you live on your own," he says. After eight
weeks of training, the older group not only increased their strength by the same
percentage as the younger group, they achieved gained strength similar to a control group
of young inactive women. But the older group's ability to increase power - force over time
- was significantly less than the younger group's; the elderly women saw only a ten
percent increase in power versus the younger women's 50 percent increase.
Colon cancer ranks second of all gastrointestinal malignant tumors, it is one of the
leading causes of cancer-related deaths worldwide. Until now, several molecules have been
reported to play an important role in gastroenterological tumorigenesis and tumor
metastasis, but the molecular mechanisms involved tumor development and progression still
remain unclear in colon cancer. A research article to be published on October 14, 2008 in
the World Journal of Gastroenterology addresses this question. In this research, by using
the combined methods of laser microdissection (LMD), P27-based RNA amplification, and
polypeptide, They evaluated differentially expressed genes between early carcinoma and
lymph node metastatic patients. Moreover, They further identified four differentially
expressed genes in the progression of colon cancer in another group of 15 patients by
means of semiquantitative reverse transcribed polymerase chain. Their result indicated
that the five gene expressions were changed in colon carcinoma cells compared with that of
controls. Of the five genes, three genes were downregulated and two were upregulated in
invasive submucosal colon carcinoma compared with non-invasive cases. The results were
confirmed at the level of RNA and gene expression. Five genes were further identified as
differentially expressed genes in the majority of cases (> 50%, 25/40) in progression
of colon cancer, and their expression patterns of which were similar to tumor suppressor
genes or oncogenes. These results not only reveal the differentially expressed genes in
progression of colon cancer, but also provide information that may prove useful for
identifying novel diagnostic and therapeutic targets.
A new insight on ethanol-induced
gastric mucosa injury
Many people all over the world indulge themselves in drinking, which is correlated to a
wide spectrum of medical, psychological, behavioral, and social problems. It is well known
that chronic alcohol abuse may induce gastrointestinal dysfunction, chronic atrophic
gastritis and is closely related with gastric carcinoma. However, the detailed mechanism
by which ethanol affects the gastrointestinal mucosa remains to be elucidated. A research
article to be published on October 14, 2008 in the World Journal of Gastroenterology
addresses this question. The research team led by Professor Ren from Gastroenterology
Division, Zhongshan Hospital of Xiamen University, systematically evaluated gastric mucosa
alteration related to ethanol. They found that the gastric mucosal lesion index was
correlated with the malondiadehyde (MDA) content in gastric mucosa. As the concentration
of ethanol was elevated and the exposure time to ethanol was extended, the contentof MDA
in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of
mitochondria was positively related to the ethanol concentration and exposure time. The
expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content
in gastric mucosa after gavage with ethanol. They concluded that Ethanol-induced gastric
mucosa injury is related to oxidative stress, which disturbs energy metabolism of
mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric
mucosa injury.
Memory function varies after damage
to key area of the brain
Scientists at the University of Liverpool have discovered dramatic differences in the
memory performance of patients with damage to the hippocampus, an area of the human brain
key to memory. The hippocampus is part of the medial temporal lobe, known to play a major
role in conscious memory. Damage to the medial temporal lobe due to illnesses such as
Herpes Simplex Encephalitis, Meningitis and Alzheimer's disease, can cause loss of
memories acquired prior to brain damage – known as retrograde amnesia - and an
inability to acquire new long-term memories – known as anterograde amnesia. However,
scientists are unsure of the exact role of the hippocampus. Some neuroscientists argue
that the hippocampus is critical for all types of conscious memory while others claim it
is only involved in recollection and that simple recognition can be performed by other
regions of the brain like the outer layer, the cortex. This is the first time that two
patients with damage restricted to this area of the brain have been assessed with the same
tests in the same lab and they were seen to show strikingly different patterns of memory
performance.
Many animals live longer when raised on low calorie diets. But now researchers at
Washington University School of Medicine in St. Louis have shown that they can extend the
life spans of roundworms even when the worms are well fed — it just takes a chemical
that blocks their sense of smell. Three years ago, the researchers, led by Kerry Kornfeld,
M.D., Ph.D., reported they found that a class of anticonvulsant medications made the
roundworm Caenorhabditis elegans live longer. But until now, they didn't quite know what
the drugs did to give the worms their longevity. They report their latest findings in the
Oct. 24 issue of the Public Library of Science Genetics. "We've learned that the
drugs inhibit neurons in the worm's head that sense chemicals in their surroundings —
the neurons are like the worm's nose," says Kornfeld, professor of developmental
biology. "Like roundworms that are grown in a food-scarce environment, the worms
exposed to the anticonvulsant ethosuximide lived longer. But these worms ate plenty of
food. That suggests that the worms' sensation of food is critical to controlling their
metabolism and life span." If roundworms sense that food is abundant, their
metabolism adjusts accordingly. Their bodies respond to promote rapid ingestion, rapid
growth and rapid aging, Kornfeld explains. In contrast, when the worms sense a shortage of
food, they make "metabolic decisions" to delay growth, delay energy use and
extend lifespan.In the long term, Kornfeld's goal is to identify compounds that could
potentially delay human aging. The research group for this project also included James
Collins, Ph.D., Kim Evason, M.D., Ph.D., Chris Pickett, Ph.D., and Daniel Schneider.
Kornfeld's lab studies C. elegans because they live only about two to three weeks, so
experimental results can be obtained quickly. In addition, the worms' genome has been
sequenced and extensively studied.
Working as part of a multi-institutional collaboration, scientists at Washington
University School of Medicine in St. Louis have assembled the most complete catalog to
date of the genetic changes underlying the most common form of lung cancer. The research,
published Oct. 23 in Nature, helps lay the foundation for more personalized diagnosis and
treatment of a disease that is the leading cause of U.S. cancer deaths. The research team
identified 26 genes that are frequently mutated in a type of cancer called lung
adenocarcinoma, a finding that more than doubles the number of genes already known to be
linked to the deadly disease. What's more, by casting a wide net in their search for
genetic alterations, the scientists are now beginning to see intriguing relationships.
They found that some of the same genes associated with lung tumors are also defective in
other cancers, that smokers and non-smokers with lung cancer have distinct genetic defects
and that several molecular pathways underlie most of the mutations.
Researchers downplay MRSA screening
as effective infection control intervention
Three Virginia Commonwealth University epidemiologists are downplaying the value of
mandatory universal nasal screening of patients for MRSA, arguing that proven,
hospital-wide infection control practices can prevent more of the potentially fatal
infections. In a report published in the November issue of Infection Control and Hospital
Epidemiology, the team, composed of internationally acclaimed epidemiologists Richard P.
Wenzel, M.D., Gonzalo Bearman, M.D., and Michael B. Edmond, M.D., of the VCU School of
Medicine, said "hospitals get more bang for their buck with evidence-based infection
control prevention."Some states, including Pennsylvania, Illinois, California and New
Jersey, are mandating nasal screening for methicillin-resistant Staphylococcus aureus, or
MRSA, in some hospitalized patients. MRSA is a strain of Staph bacteria that does not
respond to penicillin and related antibiotics, but can be treated with other drugs.
"The key safety question today, since it is possible to reduce the total risk of
hospital infections by half with a broad-based infection control program, is what is the
incremental benefit of a component focusing on a single antibiotic-resistant
pathogen?" said Wenzel. Using epidemiological principles and focusing on deadly
bloodstream infections, the team modeled a focused-screening program that was assumed to
be effective in reducing MRSA rates by 50 percent and compared it to a hospital-wide
program designed to reduce the rates of all infections by half. According to Wenzel, chair
of internal medicine at the VCU School of Medicine and immediate past president of the
International Society for Infectious Diseases, MRSA infections cause only 14 percent of
hospital infections, and investing huge resources into their control would be less
effective than implementing programs that would reduce the burden of all infections by 50
percent. Also in the model, the MRSA screening was inferior to the general infection
control programs, preventing fewer infections, fewer deaths and was also less effective in
reducing years of life lost from infections. The MRSA screening tests have false positives
– leading to the isolation of patients who are non-MRSA carriers – as well as
false negatives – missing some true carriers.
Cancer vaccine shows promise in
patients with bowel, kidney and prostate cancer
Geneva, Switzerland: Analysis of data from several phase I and II clinical trials of a new
cancer vaccine has shown it is capable of eliciting an immune response in most patients
with bowel, kidney and prostate cancer, and that it may provide clinical benefit. In a
news briefing at the 20th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer
Therapeutics in Geneva yesterday (Thursday 23 October), Dr Richard Harrop, vice-president
of clinical immunology at Oxford BioMedica, a UK-based biotechnology company – said:
"Our exploratory analyses of data from nine different trials of TroVax® demonstrate
significant associations between immune responses and overall survival in patients with
colorectal cancer, renal cancer and prostate cancer. "While it is essential that
these observations are confirmed in large, randomised studies, collectively the data
suggest that TroVax could provide some clinical benefit to cancer patients. In addition,
the data show the vaccine is well tolerated by patients." TroVax is made up of a
modified virus (Modified Vaccinia Ankara (MVA)), which acts as a vehicle to transport a
second component, a gene that produces an antigen that is present in most solid tumours,
called 5T4. TroVax is injected into patients whose solid tumours have the 5T4 tumour
antigen present, so that the vaccine can trigger the body's natural immune responses to
mobilise against 5T4. "The virus acts as both a 'vehicle' to deliver the 5T4 antigen
and as an 'adjuvant', which helps to ensure we stimulate a strong immune response to the
5T4 antigen," explained Dr Harrop. "Antibody and cellular responses can occur in
response to both the viral vector (MVA) and to the 5T4 antigen." The analysis,
presented at the symposium in Geneva, looked at data from 189 patients who had taken part
in nine trials of TroVax in the UK and USA. The patients received an average of five
injections (with a range of 1-12), and it was well tolerated by patients when given either
on its own or in combination with other anti-cancer treatments. Of 180 patients tested for
antibody responses after vaccination, 88% (159) showed positive responses to 5T4 and 98%
(176) showed positive responses to MVA. The highest levels of antibody responses were
detected after an average of two vaccinations for the MVA part of the vaccine and after
four for 5T4. Dr Harrop said: "This was expected because MVA is a foreign virus which
the immune system responds to more quickly than to a 'self antigen' such as 5T4."
European researchers have found that metastatic colorectal cancer patients with a mutation
in the BRAF gene do not respond to anti-EGFR therapy with cetuximab and panitumumab. The
finding could help doctors better identify which patients are likely to benefit from such
treatment, which is commonly used as last-effort therapy but only works in a fraction of
patients. The research was presented at the 20th EORTC-NCI-AACR [1] Symposium on Molecular
Targets and Cancer Therapeutics in Geneva today. Colorectal cancer is one of the most
common cancers worldwide and a leading cause of cancer death. Once the disease has spread,
the five-year survival rate is less than 10%. The targeted drugs cetuximab (Erbitux) and
panitumumab (Vectibix) - monoclonal antibodies that inhibit EGFR - are used to treat
patients with chemotherapy-resistant metastatic colorectal cancer. However, they are
effective in only 10-20% of such patients. Mutations in the KRAS gene explain about 30-40%
of the non-responsive cases, but the reason for the rest of the failures is unknown.
Early trial of new multi-kinase inhibitor shows impressive activity in medullary thyroid
cancer. Preliminary trials of a new multi-kinase inhibitor have indicated it has
impressive tumour shrinkage activity in patients with a difficult to treat type of thyroid
cancer. The results have put the drug’s development on a fast track, prompting the
accelerated initiation of a large phase III trial. The compound, XL184, targets cell
growth and migration, as well as blood vessel growth (angiogenesis), through inhibition of
MET kinase, VEGFR and RET kinase.
The Institute of Cancer Research and The Royal Marsden Hospital have developed a new
imaging technique which locates previously undetectable early stage cervical cancers,
according to research published in Radiology today (October 21). The pilot study, funded
by Cancer Research UK, found the new imaging technology identified small tumours, reducing
the need for radical surgery which could lead to infertility.
New promising obesity drug may have
huge potential
According to trials, a new obesity drug, Tesofensine, which may be launched on the world
market in a few years, can produce weight loss twice that of currently approved obesity
drugs. The Danish company Neurosearch and a number of researchers at the Faculty of Life
Sciences at University of Copenhagen are behind the promising findings. Tesofensine can
produce weight loss twice that of currently approved obesity drugs, and should be studied
in phase III trials. These are the conclusions of an Article published early Online and in
an upcoming edition of The Lancet, written by Professor Arne Astrup, Department of Human
Nutrition, Faculty of Life Sciences, University of Copenhagen, Denmark, and colleagues.
Increased obesity prevalence worldwide, in both developed and developing countries,
results in more people with cardiovascular disease, diabetes, musculoskeletal disorders,
and cancer. Whilst gastric bypass surgery substantially reduces bodyweight and
obesity-related disease, the researchers believe a treatment gap exists between the
effectiveness of currently marketed obesity drugs and gastric-bypass surgery. Tesofensine
– which inhibits the presynaptic uptake of the neurotransmitters noradrenaline,
dopamine and serotonin in the brain – has been shown to be safe and effective in
animal models. It also caused unintended weight loss when it was given obese patients with
Parkinson's or Alzheimer's disease when it was researched for those conditions. The drug
works by suppressing hunger, leading to an energy deficit which burns off excess body fat.
This randomised, placebo-controlled phase II study was done in five Danish obesity
management centres, and involved 203 obese patients (body mass index 30-40 kg/m2),
weighing a mean of just over 100kg. They were prescribed a limited-energy diet and
assigned to tesofensine 0.25mg (52 patients), 0.5 mg (50), 1.0 mg (49), or placebo (52),
all once daily for 24 weeks. The primary outcome was percentage change in bodyweight. A
total of 161 patients completed the study, and an analysis showed that the mean weight
loss recorded for placebo and diet was 2.2kg and for tesofensine 0.25mg, 0.5mg and 1.0mg
it was 6.7kg, 11.3kg, and 12.8kg respectively. For the 0.5mg and 1.0mg doses, this
represented a weight loss around twice that attained using sibutramine or rimonabant*, the
currently-approved therapies in Europe. Blood pressure was increased in the 1.0mg
group.The most common side-effects caused by tesofensine were dry mouth, nausea,
constipation, hard stools, diarrhoea, and insomnia. The authors conclude that the 0.5mg
dose of tesofensine is more promising than the 1.0mg dose because it produces a similar
weight loss with less side-effects. They say: "We conclude that tesofensine 0.5 mg,
once daily for 6 months, has the potential to produce twice the weight loss as currently
approved drugs; however, larger phase III studies are needed to substantiate our
findings."
CU-Boulder research finds link
between physical and interpersonal warmth
Do people trust others more when they experience physical warmth? That's the theory of
CU-Boulder Assistant Professor Lawrence E. Williams, who says simply handling a hot cup of
coffee can change one's attitude toward a stranger. In a paper published in the Oct. 24
issue of Science, Williams details a study he conducted with Yale University's John A.
Bargh that shows a link between the way unsuspecting subjects rated a hypothetical
person's personality and whether or not they had held a warm or cold beverage just prior
to the test. "The basic scientific implication is about exploring the link between
the physical world and the psychological world," said Williams, an assistant
professor of marketing at CU's Leeds School of Business. "It's at the same time
subtle and very powerful -- a repeated association of physical warmth that is learned over
a lifetime."Williams asserts that people naturally speak about others being
"warm" or "cold," and prefer to spend time with those they perceive as
"warm." "When we use these terms, we're not really concerned with physical
temperature, but our findings suggest that our dual use of the word "warm" is
neither haphazard nor accidental." For the experiment, Williams enlisted the help of
a confederate, who escorted the test subjects from the lobby of a psychology building and
rode the elevator to the test area with them. The confederate carried a clipboard, two
textbooks and a cup of hot or iced coffee and knew nothing of the hypothesis being tested.
During the trip to the test area, the confederate asked the subject to hold the cup of
coffee while she recorded their name and the time of their participation. Holding the hot
cup, Williams hypothesized, would prime the subject to have a more positive appraisal of a
hypothetical person they read about once they reached the testing room. And according to
his data, Williams was right: People who had briefly held the hot coffee cup perceived the
target person as being significantly "warmer" than did those who had briefly
held the cup of iced coffee.
New CU-Boulder Study Shows
Diversity Decreases Chances of Parasitic Disease
A new University of Colorado at Boulder study showing that American toads who pal around
with gray tree frogs reduce their chances of parasitic infections known to cause limb
malformations has strong implications for the benefits of biodiversity on emerging
wildlife diseases. The experiments showed that when the toad tadpoles were raised in tanks
with the parasitic trematodes -- tiny worms whose larvae burrow into tadpole limb regions
and disrupt normal leg development -- 40 percent of the emerging frogs became deformed,
said CU-Boulder Assistant Professor Pieter Johnson. But when the toad tadpoles were joined
in the tanks with gray tree frog tadpoles, parasitic infections in the toads dropped by
almost half, said Johnson, lead author of the study. The study showed tree frog tadpoles
acted as "sponges" for the trematode parasites, which were subsequently killed
by the immune systems of frog tadpoles, said Johnson. As a result, fewer parasites were
available to infect and cause malformations in the toads. Both the gray tree frog and
American toad are broadly distributed in the Midwest and eastern United States and often
occur in the same wetlands, he said. "This is one of the first experimental studies
to definitively show that an increase in diversity of host species actually can reduce
parasite transmission and disease," said Johnson of CU-Boulder's ecology and
evolutionary biology department. Published in the October issue of Ecology Letters, the
study has implications for the declining global diversity of wildlife species that are
susceptible to parasitic infections, said Johnson. Other research has shown that a
decrease in diversity in mammal host species for ticks carrying Lyme disease increases the
risk of Lyme disease in humans, Johnson said. Similar relationships between wildlife
diversity and disease prevalence have been suggested by other researchers to influence
other vector-borne diseases, including West Nile virus, tick-borne encephalitis and
bubonic plague, he said.
Gladstone scientists find potential
strategy to eliminate poisonous protein from Alzheimer brains
Scientists at the Gladstone Institute of Neurological Disease (GIND) have identified a new
strategy to destroy amyloid-beta (AB) proteins, which are widely believed to cause
Alzheimer's disease (AD). Li Gan, PhD, and her coworkers discovered that the activity of a
potent AB-degrading enzyme can be unleashed in mouse models of the disease by reducing its
natural inhibitor cystatin C (CysC). All of us produce AB proteins in the brain. However,
in most people, the proteins never build up to dangerous levels because they are cleared
away by enzymes that destroy them. Previously Dr. Gan's laboratory had shown that
cathepsin B (CatB) is such an AB-degrading enzyme. In the latest issue of the journal
Neuron, the researchers report a highly effective approach to promote CatB-mediated
clearance of AB . "Many groups have developed drugs to block the production of AB,
but the efficacy and safety of this approach remains to be demonstrated in clinical
trials," said GIND Director Lennart Mucke, MD "By identifying an effective
strategy to enhance the removal of AB, this research provides a very promising alternative
or complementary therapeutic avenue." High levels of AB in the brain may result from
overproduction of AB or from an inability to eliminate it from the brain. While most work
has focused on the first option, the latter has been problematic. For example, efforts to
develop a vaccine that would trigger the immune system to eliminate AB have shown limited
success and resulted in adverse side effects. "Our strategy to harness the activity
of a powerful AB-degrading enzyme takes advantage of the brain's own defense system to
remove the toxic AB build-up," said Dr. Gan. "In principle, one could boost the
activity of CatB by expressing more of it in the brain or by reducing the activity of
CysC, its natural inhibitor. We focused on the latter strategy because it has greater
long-term therapeutic potential." Many enzymes that degrade proteins are kept in
check by regulators called protease inhibitors. The activity of CatB is regulated by the
protease inhibitor CysC. By reducing CysC activity, the scientists were able to unleash
the AB-degrading power of CatB, effectively preventing the build-up of AB in mouse models
of AD.
If your systolic stinks, 'rotten
egg' gas may be why
Anyone with a nose knows the rotten-egg odor of hydrogen sulfide, a gas generated by
bacteria living in the human colon. Now an international team of scientists has discovered
that cells inside the blood vessels of mice — as well as in people, no doubt —
naturally make the gassy stuff, and that it controls blood pressure. Having discovered
that hydrogen sulfide, or H2S, is produced in the thin, endothelial lining of blood
vessels, the researchers, including scientists from Johns Hopkins, report today in Science
that H2S regulates blood pressure by relaxing blood vessels. As the newest member of a
family of so-called gasotransmitters, this messenger molecule is akin in function, if not
form, to chemical signals like nitric oxide, dopamine and acetylcholine that relay signals
between nerve cells and excite or put the brakes on mind-brain activities. "Now that
we know hydrogen sulfide's role in regulating blood pressure, it may be possible to design
drug therapies that enhance its formation as an alternative to the current methods of
treatment for hypertension," says Johns Hopkins neuroscientist Solomon H. Snyder,
M.D., a co-author of the paper. Conducting their investigations using mice missing a gene
for an enzyme known as CSE, long suspected as responsible for making H2S, the researchers
first measured hydrogen sulfide levels in a variety of tissues in the CSE-deficient mice
and compared them to normal mice. They found that the gas was largely depleted in the
cardiovascular systems of the altered mice, engineered by Rui Wang, M.D., Ph.D., of
Lakehead University in Ontario, and Lingyun Wu, M.D., Ph.D., of the University of
Saskatchewan, Canada. By contrast, normal mice had higher levels — clear evidence
that hydrogen sulfide is normally made by mammalian tissues using CSE. Next, the
scientists applied tiny cuffs to the tails of the mice and measured their blood pressure,
noting spikes of about 20 percent, comparable to serious hypertension in humans.
Sudden Cardiac Death Number One
Risk for Patients on Dialysis
Inflammation, malnutrition identified as key risk factors. In a 10-year study of more than
a thousand kidney failure patients, sudden cardiac death emerged as the number one cause
of death for patients on dialysis, according to a Johns Hopkins researcher. The study,
already published online and appearing in the Nov. 2 issue of Kidney International,
identified systemic inflammatory response and malnutrition as key risk factors for the
fatal heart attacks. “This is believed to be the first time anyone has taken a
rigorous prospective look at why so many patients on dialysis die from sudden cardiac
death, and the results could help doctors identify those at highest risk and potentially
save lives,” says Rulan S. Parekh, M.D., associate professor in the Department of
Nephrology at the Johns Hopkins University School of Medicine. Parekh and her team
gathered their data from the Choices for Healthy Outcomes In Caring for ESRD (CHOICE)
cohort of 1,041 end-stage renal disease (ESRD) patients on dialysis. In a 9.5-year period,
658 of this group died. The largest number of these deaths, 146, were the result of sudden
cardiac death (SCD), in this case unexpected deaths that occurred outside of the hospital
setting.
Depression during pregnancy can
double risk of preterm delivery
Depressed pregnant women have twice the risk of preterm delivery than pregnant women with
no symptoms of depression, according to a new study by the Kaiser Permanente Division of
Research. The study is published online in the Oxford University Press's journal Human
Reproduction on behalf of the European Society of Human Reproduction and Embryology. The
study found that pregnant women with symptoms of depression have an increased risk of
preterm delivery, and that the risk grows with the severity of the depressive symptoms.
These findings also provide preliminary evidence that social and reproductive risk
factors, obesity, and stressful events may exacerbate the depression-preterm delivery
link, according to the researchers. Because the majority of the women in the study did not
use anti-depressants, the study provides a clear look at the link between depression and
preterm delivery. The study -- which is among the first to examine depression and pre-term
delivery in a representative and diverse population in the United States -- looked at 791
pregnant Kaiser Permanente members in San Francisco city and county from October 1996
through October 1998.
