News 2 april 2009
Health Benefits, Consequences of
Folic Acid Dependent on Circumstances
For the past several decades, evidence has
shown that greater dietary intake of the B-vitamin, folate, offers protection against the
development of certain common cancers and reduces neural tube defects in newborns, opening
new avenues for public health interventions that have a great impact on health. However,
folate’s central role as an essential factor in DNA synthesis also means that
abundant availability of the vitamin can enhance the development of pre-cancerous and
cancerous tumors. Further, the intake of folic acid that results from consuming foods that
are voluntarily fortified (e.g.: ready-to-eat cereals) in combination with the additional
intake received from mandatory fortification of flour means that supplementary intake of
folic acid is unnecessary for many segments of the population, and may even present a
risk. Nevertheless, the issue is a complicated one since women of child-bearing age seem
to benefit from supplemental folic acid in regard to its protection against birth defects.
In the April issue of the journal Nutrition Reviews, two new articles by Omar Dary, Ph.D.,
and Joel B. Mason, M.D., assess the conditions under which folic acid can be beneficial
and harmful and contribute to guidelines for the healthful intake of folic acid as a
complement to dietary folate. The consequences of inadequate folate intake remain
prevalent in many countries, even in industrial countries where specific interventions of
folic acid have not been implemented. Moreover, there continues to be some
concern—which, to date, lacks compelling scientific evidence—that the synthetic
form of the vitamin, folic acid, might have adverse effects that do not exist with natural
sources of folate. Under most circumstances, adequate intake of folate appears to assume
the role of a protective agent against cancer, most notably colorectal cancer. However, in
select circumstances in which an individual who harbors a pre-cancerous or cancerous tumor
consumes too much folic acid, the additional amounts of folate may instead facilitate the
promotion of cancer. In countries in which the fortification of flour with folic acid is
working well, additional supplementation in the form of vitamin pills can lead to
excessive intakes of the vitamin, which can then have undesirable adverse effects.
Prolactin reduces fat metabolism
The hormone prolactin is necessary for the
production of breast milk, but it also affects adipose (fatty) tissue and the body’s
metabolism. This has been shown by a thesis from the Sahlgrenska Academy, University of
Gothenburg, Sweden. Raised prolactin levels in a woman who is not pregnant or breast
feeding reduces lipid (fat) metabolism. Over 30 000 Swedish men and women may have raised
levels of prolactin. Women who are pregnant or breast feeding have naturally raised levels
of prolactin, but stress, some medicines and benign brain tumours can also lead to raised
levels of the hormone. In many cases doctors don’t know what causes the rise in
hormone levels. In women, an abnormally high level can cause menstrual disturbances and
infertility, and may also result in insulin resistance. “In recent years scientists
have also recognised the role of prolactin in the development of obesity, but little
research has been done into the precise mechanism by which prolactin regulates
metabolism,” says Louise Nilsson.
In her thesis Louise Nilsson shows that there are receptors for the breast feeding hormone
in human fatty tissue.
Diabetes Drug Class Linked to
Vision-Threatening Complication
Treatment with the glitazone class of
diabetes drugs leads to a "modest" increase in the risk of diabetic macular
edema (DME)—a common complication that can lead to vision loss, reports a study in
the April issue of the American Journal of Ophthalmology, published by Elsevier. Using a
database of about 170,000 patients with diabetes, Drs. Donald S. Fong and Richard
Contreras of Southern California Permanente Medical Group analyzed the link between
glitazones and the development of DME. Diabetic macular edema is a common diabetes
complication, with swelling and fluid build-up in the retina leading to progressive visual
loss. The researchers identified 996 patients who were diagnosed with DME during 2006.
Overall, patients who took glitazones were 2.6 times more likely to develop DME than
patients not taking these drugs. Even after further adjustment for other factors, DME risk
remained 60 percent higher for glitazone users. Previous studies have linked glitazones to
problems related to fluid retention and edema (swelling), including heart failure. Fluid
retention from heart failure or other diseases can worsen DME. Most of the glitazone users
in the study were taking pioglitazone (Actos). Other studies have linked rosiglitazone
(Avandia)—the only other approved glitazone drug—to a possible increase in the
risk of myocardial infarction.
Coming face to face with autism
In the first study of its kind researchers
will use video clips of spontaneously produced facial expressions in a real life social
context to explore emotion recognition in autism. This research, carried out at The
University of Nottingham, will go beyond the more artificial emotion recognition tasks
that have previously been used. The eye movements of volunteers will also be tracked to
find out which areas of the face were looked at while volunteers make spontaneous
judgements. The study is being conducted by PhD student Sarah Cassidy who is a member of
the Autism Research Team based in the School of Psychology. Her work has been funded
through a PhD studentship from the Economic and Social Research Council. Her work will
investigate if people with autism look at faces, particularly in the eye region,
differently. If so, does this have any relationship with their ability to recognise
emotions in others? What is their understanding of emotions in different social contexts?
And as a consequence, how difficult is it for them to socialise and communicate with other
people? Sarah said: “Previous research has suggested that people with autism have
difficulty inferring emotion from faces due to lack of attention to the eyes and increased
attention to the mouth. However not all studies have shown differences in emotion
recognition and eye gaze. There is also little research asking what role reading emotion
from the eyes plays in social communication difficulties in autism, with a few studies
suggesting a relationship with social competence and responsiveness.”
Einstein scientists propose new
theory of autism
Scientists at Albert Einstein College of
Medicine of Yeshiva University have proposed a sweeping new theory of autism that suggests
that the brains of people with autism are structurally normal but dysregulated, meaning
symptoms of the disorder might be reversible. The central tenet of the theory, published
in the March issue of Brain Research Reviews, is that autism is a developmental disorder
caused by impaired regulation of the locus coeruleus, a bundle of neurons in the brain
stem that processes sensory signals from all areas of the body. The new theory stems from
decades of anecdotal observations that some autistic children seem to improve when they
have a fever, only to regress when the fever ebbs. A 2007 study in the journal Pediatrics
took a more rigorous look at fever and autism, observing autistic children during and
after fever episodes and comparing their behavior with autistic children who didn't have
fevers. This study documented that autistic children experience behavior changes during
fever. "On a positive note, we are talking about a brain region that is not
irrevocably altered. It gives us hope that, with novel therapies, we will eventually be
able to help people with autism," says theory co-author Mark F. Mehler, M.D.,
chairman of neurology and director of the Institute for Brain Disorders and Neural
Regeneration at Einstein. Autism is a complex developmental disability that affects a
person's ability to communicate and interact with others. It usually appears during the
first three years of life. Autism is called a "spectrum disorder" since it
affects individuals differently and to varying degrees. It is estimated that one in every
150 American children has some degree of autism. Einstein researchers contend that
scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA)
system as being involved in autism. "The LC-NA system is the only brain system
involved both in producing fever and controlling behavior," says co-author Dominick
P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein.
The locus coeruleus has widespread connections to brain regions that process sensory
information. It secretes most of the brain's noradrenaline, a neurotransmitter that plays
a key role in arousal mechanisms, such as the "fight or flight" response. It is
also involved in a variety of complex behaviors, such as attentional focusing (the ability
to concentrate attention on environmental cues relevant to the task in hand, or to switch
attention from one task to another). Poor attentional focusing is a defining
characteristic of autism.
MDC researchers prevent virus
induced myocarditis
Life-threatening cardiac arrhythmia can be
a consequence of myocarditis – an inflammation of the cardiac muscle that can be
caused by the Coxsackievirus. In mice, Dr. Yu Shi, Chen Chen, and Professor Michael
Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany,
have now abolished the infection by blocking the receptor which is required for virus
entry. "We did not detect a single cardiomyocyte that was infected by the virus.
Inflammation of the heart muscle associated with this virus infection did not
develop," Dr. Shi said. (Journal of American College of Cardiology, 2009;
53:1219-1226, doi:10.1016/j.jacc.2008.10.064).* The receptor used by the Coxsackievirus to
infect the heart is the Coxsackie-adenovirus-receptor (CAR). It can be found in the cell
membrane of myocardial fibers. Ulrike Lisewski, Dr. Shi, Michael Radke, and Prof.
Gotthardt discovered only recently that CAR is necessary for a regular heart beat. In
their current study, the researchers could demonstrate that genetically engineered mice
without CAR were protected from cardiac infection caused by the Coxsackievirus. Moreover,
the mice did not show any evidence of inflammatory cardiomyopathy. That is why Professor
Gotthardt assumes – contrary to previous hypotheses – that the direct effects of
the virus infection, and not the autoimmune response, primarily determine the disease
process. This distinction is important in order to develop effective methods for future
therapies of viral myocarditis. One therapeutic option could be to use CAR as a drug
target and to block this receptor with a pharmacological agent.
Autism linked with stress hormone
levels
Some of the symptoms of the autistic
condition Asperger Syndrome, such as a need for routine and resistance to change, could be
linked to levels of the stress hormone cortisol, suggests new research led by the
University of Bath. Normally, people have a surge of this hormone shortly after waking,
with levels gradually decreasing throughout the day. It is thought this surge makes the
brain alert, preparing the body for the day and helping the person to be aware of changes
happening around them. However, a study led by Dr Mark Brosnan and Dr Julie Turner-Cobb
from the Department of Psychology at the University of Bath, and Dr David Jessop from the
University of Bristol, has found that children with Asperger Syndrome (AS) do not
experience this surge.The researchers believe these findings may help to explain why
individuals with this condition have difficulties with minor changes to their routine or
changes in their environment. The study has been published in the peer-reviewed journal
Psychoneuroendocrinology. Dr Brosnan explained "Cortisol is one of a family of stress
hormones that acts like a 'red alert' that is triggered by stressful situations allowing a
person to react quickly to changes around them.
"In most people, there is a two-fold increase in levels of this hormone within 30
minutes of waking up, with levels gradually declining during the day as part of the
internal body clock.
"Our study found that the children with AS didn't have this peak although levels of
the hormone still decreased during the day as normal.
Some radiation therapy treatments
can decrease fertility
In female cancer patients of reproductive
age, radiation treatment directly to the ovaries should be avoided because there is a
direct relationship between certain types of radiation therapy and fertility problems,
according to a review in the April 1 issue of the International Journal of Radiation
Oncology*Biology*Physics, the official journal of the American Society for Radiation
Oncology (ASTRO).
Radiation therapy to the pelvic region can cause ovarian failure or result in damage that
makes the uterus unable to accommodate the growth of a fetus. These effects are not a
great concern to cancer patients past their reproductive years, but due to the growing
number of pediatric and young-adult cancer survivors, these effects are increasingly
relevant. Researchers at the Harvard Radiation Oncology Program and the Department of
Radiation Oncology at Brigham and Women's Hospital and Dana-Farber Cancer Institute, both
in Boston, sought to review the impact of radiation therapy on fertility, pregnancy and
neonatal outcomes among female patients and the effectiveness of ovarian transposition, or
moving the ovaries out of the field of radiation, as a means of preserving fertility. The
study authors reviewed the outcomes of past studies that reported fertility, pregnancy and
neonatal outcomes as a result of cranio-spinal, abdominal and pelvic radiation and
determined that cranio-spinal irradiation caused hormonal changes that affected a woman's
ability to become pregnant later in life. Women who received abdominal or pelvic radiation
had an increased risk of uterine dysfunction that lead to miscarriage, preterm labor, low
birth weight and placental abnormalities. The study also determined that women who
received low doses of ovarian radiation can suffer early menopause.
New evidence explains poor infant
immune response to certain vaccines, says MU researcher
For years, researchers and physicians have
known that infants' immune systems do not respond well to certain vaccines, thus the need
for additional boosters as children develop. Now, in a new study from the University of
Missouri, one researcher has found an explanation for that poor response. In the study,
the MU scientist found evidence that the immune systems of newborns might require some
time after birth to mature to a point where the benefits of vaccines can be fully
realized. Habib Zaghouani, a professor of molecular microbiology and immunology and child
health at the MU School of Medicine, recently found that a slowly maturing component of
the immune system might explain why newborns contract infections easily. In his work,
Zaghouani studied newborn mice and how their immune systems reacted when they were
repeatedly exposed to an antigen that simulates a virus. Zaghouani found that while the
antigen would prompt a response of the immune system, it was not the expected response. In
the adult immune system, two major types of cells, known as T-helper 1 (Th-1) and T-helper
2 (Th-2) cells, are instrumental in the development of an effective immune response.
Typically, Th-1 cells respond when dangerous microbes enter the body. The Th-1 cells then
work to help destroy the foreign microbes. When an antigen from a vaccine enters a body
with a mature immune system, Th-1 cells respond and, after destroying the invader, the
Th-1 cells "remember" how to fight the antigen for future battles. Th-2 cells
typically develop when the body is exposed to allergens. The responses of Th-2 cells are
usually strong and manifest in the form of allergic reactions. When Zaghouani gave the
newborn mice an antigen shortly after birth, he noticed the presence of both Th-1 and Th-2
cells. However, when he gave the antigen a second time, he noticed an abundance of Th-2
cells that responded to the antigen instead of Th-1 cells. Zaghouani was surprised to
notice that the Th-2 cells worked to destroy the small contingent of Th-1 cells that had
responded to the antigen given at birth. "Perhaps we should test vaccines at a very
early age in animals to establish a regimen with the most effectiveness," Zaghouani
said.
UC Davis researchers identify a
protein that may help breast cancer spread, beat cancer drugs
New research from UC Davis Cancer Center
shows that a protein called Muc4 may be the essential ingredient that allows breast cancer
to spread to other organs and resist therapeutic treatment. The study, which appears in
the April 1 issue of Cancer Research, is one of the first to characterize the role of Muc4
in the disease. Kermit Carraway, senior author of the study, knew that Muc4 was not always
expressed in primary breast cancer tumors, yet it could be present in lymph node
metastases. He suspected that it may have a specialized function in the process of
metastasis. "Breast cancer deaths are caused by metastasis, not by the primary
tumor," explained Carraway, an associate professor of biochemistry and molecular
medicine. "It's at that point that the disease also becomes difficult to treat. We
think that Muc4 may be packing a one-two punch by promoting the release of breast cancer
cells from the primary tumor and then inhibiting their death." Muc4 is member of a
group of proteins called mucins, which are commonly found in fluids such as tears and
mucus. They have a known role in protecting epithelial cells, from which breast cancer
cells are derived. When separated from their surrounding cell matrix, epithelial cells
tend to die. Metastasizing breast cancer cells, however, can survive this detachment.
"Because breast cancer cells can lose their adhesive properties and still thrive, we
suspected that Muc4 may be somehow allowing them to leave their cellular framework, travel
to secondary sites and withstand treatment," Carraway explained. To test his
suspicions, Carraway and his team conducted two experiments. They started by comparing
breast cancer cells that express Muc4 with those for which Muc4 production is blocked. The
researchers then exposed both types of cells to chemotherapy drugs. The Muc4-producing
cells survived. They repeated the experiment with breast cancer cells and epithelial cells
that do not naturally express Muc4 but were engineered to do so. Both sets of cells
avoided cell death and effectively resisted chemotherapy."Our results lead us to
believe that Muc4 is somehow disrupting normal links between epithelial cells," said
UC Davis graduate student Heather Workman, lead author of the study. "We now need to
refine our understanding of this disruption process in order to find ways to interfere
with it. There currently are no drugs that target Muc4, and this research will help change
that."
