News 1 april 2009
By Shutting Down Inflammation,
Agent Reverses Damage from Spinal Cord Injury in Preclinical Studies
Researchers at Georgetown University
Medical Center (GUMC) have been able to speed recovery and substantially reduce damage
resulting from spinal cord injury in preclinical studies. Their research, published online
in Annals of Neurology and led by Kimberly Byrnes, PhD, shows that inflammation following
injury causes the neurotoxicity that leads to lasting nerve cell damage, and that an
experimental agent is able to block this inflammatory reaction. “The findings we have
made in this study may potentially be applicable to other neurological disorders,
including stroke, head injury, Alzheimer’s disease and Parkinson’s
disease,” says senior investigator Alan I. Faden, MD, a professor of neuroscience and
director of the Laboratory for the Study of Central Nervous System Injury at GUMC. Faden
says that the experimental agent they tested (CHPG), an activator of a type of glutamate
receptor, is not ideal for human use because it cannot easily penetrate the blood-brain
barrier. But he adds, “now that we know the biological target, a new drug could be
designed that is better suited for clinical treatment of these neurodegenerative
disorders.” CHPG shuts down activation of key immune cells in the brain known as
microglia, which sense pathogens or damage in the spinal cord and brain. They helpfully
foster the destruction of microbial invaders and clean up biological detritus that occurs
after an injury, but researchers say they have a dark side as well – they can worsen
the damage by releasing toxic inflammatory factors.
Physical activity may strengthen
children's ability to pay attention
As school districts across the nation
revamped curricula to meet requirements of the federal “No Child Left Behind”
Act, opportunities for children to be physically active during the school day diminished
significantly. Future mandates, however, might be better served by taking into account
findings from a University of Illinois study suggesting the academic benefits of physical
education classes, recess periods and after-school exercise programs. The research, led by
Charles Hillman, a professor of kinesiology and community health and the director of the
Neurocognitive Kinesiology Laboratory at Illinois, suggests that physical activity may
increase students’ cognitive control – or ability to pay attention – and
also result in better performance on academic achievement tests. “The goal of the
study was to see if a single acute bout of moderate exercise – walking – was
beneficial for cognitive function in a period of time afterward,” Hillman said.
“This question has been asked before by our lab and others, in young adults and older
adults, but it’s never been asked in children. That’s why it’s an important
question.” For each of three testing criteria, researchers noted a positive outcome
linking physical activity, attention and academic achievement. Study participants were
9-year-olds (eight girls, 12 boys) who performed a series of stimulus-discrimination tests
known as flanker tasks, to assess their inhibitory control.
Genetic Link Uncovered in Disparate
Colon Cancer Death
A new study reveals the first-ever genetic
link to the reason African-Americans are at increased risk of dying from colon cancer. The
discovery by researchers at the University of Alabama at Birmingham (UAB) is focused on a
protein variant called Pro72 identified through genetic testing. In the study,
African-Americans with a Pro72 protein variant had more than double the risk of dying from
an advanced form of colon cancer compared to whites, the researchers said.The discovery
boosts the scientific understanding of racial disparities in cancer and other diseases and
adds new detail in the ongoing search for more personalized cancer-fighting therapies,
said Upender Manne, Ph.D., an associate professor in the UAB Department of Pathology who
led the study.
Light reveals breast tumor oxygen
status
Light directed at a breast tumor through a
needle can provide pathologists with biological specifics of the tumor and help
oncologists choose treatment options that would be most effective for that individual
patient. Duke University bioengineers have developed a light-based system that can quickly
and easily provide important information about oxygen levels within a tumor while it is
still in place. The new system, based on diffuse reflectance spectroscopy, gives
researchers important clues about the tumor by interpreting how the light is either
reflected back from the tumor or absorbed. Oxygen status is important, the researchers
said, since past studies have shown that low levels of oxygen, or hypoxia, are more often
associated with malignant tissue than healthy normal tissue. Tumors that thrive in these
low-oxygen environments tend to be more difficult to treat, the researchers said. "We
developed an easy-to-use fiber-optic probe that can provide immediate and non-destructive
measurements of tumor oxygenation," said J. Quincy Brown, a fourth-year post-doctoral
fellow in the laboratory of Nirmala Ramanujam, associate professor of biomedical
engineering at Duke's Pratt School of Engineering. The results of the Duke experiments
were published April 1 in the journal Cancer Research. "This new approach could be an
important new tool for physicians in determining the aggressiveness of a specific tumor
and which therapies might work best against it," Brown said. "Since this system
is compatible with commonly used biopsy needles, we could make oxygen measurements at the
time of a needle biopsy, providing immediate feedback about the tumor's oxygen
concentration."
The More Oral Bacteria, the Higher
the Risk of Heart Attack, UB study shows.
Several studies have suggested there is a
connection between organisms that cause gum disease, known scientifically as periodontal
disease, and the development of heart disease, but few studies have tested this theory. A
study conducted at the University at Buffalo, where the gum disease/heart disease
connection was uncovered, now has shown that two oral pathogens in the mouth were
associated with an increased risk of having a heart attack, but that the total number of
germs, regardless of type, was more important to heart health. Results of the study will
be presented during a poster session at the International Association of Dental Research
(IADR) General Session being held in Miami, Fla., from April 1-4. Oelisoa M. Andriankaja,
D.D.S., Ph.D., conducted the study in UB's Department of Oral Biology in the School of
Dental Medicine, as a postdoctoral researcher. She currently is an adjunct professor at
the University of Puerto Rico's School of Dental Medicine. "The message here,"
said Andriankaja, "is that even though some specific periodontal pathogens have been
found to be associated with an increased risk of coronary heart disease, the total
bacterial pathogenic burden is more important than the type of bacteria.
Weight at birth tied to heart
disease and diabetes risk in adulthood
Lower weight at birth may increase
inflammatory processes in adulthood, which are associated with chronic diseases such as
heart disease and diabetes, according to a new study accepted for publication in The
Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM). Both the
fetal and infancy periods are sensitive, critical stages of growth and development.
Studies have previously suggested babies with lower weight at birth are at a higher risk
for developing chronic diseases but until now, there has been little understanding to
explain why. This study suggests an association between lower weight at birth and
inflammation in adulthood may provide that explanation. Inflammation is a normal
physiologic response of the body, and serves as a host defense which provides protective
response to infection or tissue injury. If the source of infection or injury is not
repressed, low-grade inflammation can persist and may promote the development of heart
disease or diabetes. Earlier studies have found that babies born small for gestational age
have weak immune systems, but at six years old have more white blood cells than babies
born at a normal weight. White blood cells are cells of the immune system that defend the
body against both infectious disease and foreign materials. These findings suggest that
age might amplify the association between early growth and inflammatory processes. In this
study, researchers followed 5,619 children born in 1966 and followed them up until they
reached adulthood. As compared to children with 'normal' weight in the first year of life,
researchers observed that babies born relatively smaller and gained the least weight
during infancy had a higher number of white blood cells, an indicator of inflammation, in
adulthood.
Balancing hormones may help prevent
preterm births
The relationship between two different
types of estrogen and a hormone produced in the placenta may serve as the mechanism for
signaling labor, according to a new study accepted for publication in The Endocrine
Society's Journal of Clinical Endocrinology & Metabolism (JCEM). This finding may help
doctors intervene and prevent preterm birth much more effectively. "The trigger for
the onset of labor in women has been a puzzle for a long time," says Dr. Roger Smith,
MD, PhD, of John Hunter Hospital in Newcastle, Australia and lead author of the study.
"Our findings show we may have an answer, and furthermore may be able to delay or
advance labor." Humans have two types of estrogen called estradiol (E2) and estriol
(E3). When E2 and E3 are in roughly equal amounts there is no drive to labor, but the
opposite holds true once one becomes in greater excess than the other. This study
evaluated the ratio of E3 to E2 in 500 pregnant women and found that it went up rapidly as
labor approached indicating that E3 could stimulate the onset of labor. Dr. Smith and his
colleagues then sought to understand what was causing the increase in E3 and they believe
they found an answer. In a previous study they showed that a hormone in the placenta,
called corticotrophin-releasing hormone (CRH), rises rapidly through pregnancy, peaking at
the time of labor. CRH levels rise earlier in women who deliver prematurely and later in
women who deliver late, forming a biological clock that regulates the length of pregnancy.
Researchers also showed that CRH can act on the adrenal glands of the fetus to stimulate
the production of a steroid hormone which the placenta uses to make E3. This study showed
a strong relationship between CRH levels in the mother's blood in the weeks before birth
and the levels of E3 supporting the view that CRH increases E3. "CRH may be the
catalyst for the onset of labor, by driving steroid hormone production in the fetus, which
then leads to an increase in E3 so that it exceeds E2," said Dr. Smith. "If this
progression is correct, it may explain why women with a baby who dies in utero can still
go into labor. In this scenario, levels of E3 would drop making E2 more dominant and
triggering the onset of labor."
Researchers find marker for
severity in adult brain cancer
Researchers at UT Southwestern Medical
Center have identified a new biological indicator that may help identify which
brain-cancer patients have the most aggressive forms of the disease. The researchers found
that an inflammation-related molecule called RIP1 is commonly found in high levels in
glioblastoma, the most common primary malignant brain tumor in adults. The protein RIP1 is
a component of the complex NF-kB signaling network — a family of proteins that play a
key role in inflammation-induced cancer.The study, available online and published in the
April issue of Cancer Research, could provide a new target for therapeutic drugs for
glioblastoma patients who have a high level of RIP1 in their tumors coupled with NF-kB
activation. “This is the first report of high RIP1 levels being associated with any
type of cancer,” said Dr. Amyn Habib, assistant professor of neurology at UT
Southwestern and the study’s senior author. “Our data suggests that increased
expression of RIP1 could serve as a marker to identify patients who have a significantly
worse prognosis and who will likely be resistant to chemotherapy.”
Compassion fatigue - Impact on
healthcare providers of caring for the terminally ill
Compassion fatigue in nurses, doctors and
other front line cancer-care providers significantly impacts how they interact with
patients, with patient families, with other healthcare workers, and with their own family,
according to analysis by Indiana University School of Medicine and Regenstrief Institute
researchers published in the March issue of the Journal of Health Psychology. "The
healthcare field is becoming more aware of the profound emotional disturbances that occur
in healthcare providers when they witness the suffering and pain of their patients in the
face of an incurable disease, such as cancer. Healthcare providers are often partners in
this journey, and the understanding of the effects of caring for the terminally ill on the
caregiver is limited," the researchers wrote. They reviewed 57 studies to identify
the prevalence of compassion fatigue among cancer-care providers, how to detect it and
means of prevention and treatment. "Individuals who are drawn into healthcare careers
may be more likely to develop compassion fatigue, based on their drive for perfection and
to do their best for their patients. If you work in an environment where despite your very
best efforts patients for whom you provide care will not survive, there is a set up for
developing a sense of 'there is nothing I can do anymore,'" says the study's
principal investigator Caroline Carney Doebbeling, M.D., associate professor of medicine
and of psychiatry at the IU School of Medicine and a Regenstrief Institute research
scientist. The term compassion fatigue was first coined in the 1990s to describe a
syndrome experienced by a healthcare provider caring for individuals facing dire
consequences as a result of their disease. Going beyond empathy or "feeling bad"
for the person, it effects the nurse, doctor or other member of the healthcare team in a
way that he or she often develops a distance from the patient as a way of self-protection.
Symptoms of compassion fatigue include chronic tiredness and irritability, lack of joy in
life, engagement in behaviors which are fine in moderation, such as drinking, at a
destructive level. Like individuals who have post traumatic stress disorder (PTSD), those
with compassion fatigue often re-experience the deaths of their patients, according to Dr.
Carney Doebbeling. Compassion fatigue can lead individuals to protect or insulate
themselves by loss of compassion, cynicism, boredom, decreased productivity, more sick
days and ultimately higher turnover. "How do you deal with compassion fatigue if you
see patients every single day?" asks Dr. Carney Doebbeling. "In order to provide
the best care to patients, the system, beginning with training in nursing and medical
schools and residency, has to do a better job of helping those who go into cancer care
learn what to expect and how to deal with it. On the job we need to create supportive work
environments where supervisors and colleagues are aware that those who care for the
sickest of the sick may be vulnerable to the triggers that could bring about compassion
fatigue." While compassion fatigue has not been labeled a psychiatric disorder, it
can lead to depression and anxiety disorders, according to Dr. Carney Doebbeling, a member
of the Indiana University Melvin and Bren Simon Cancer Center, who is an internist and a
psychiatrist as well as a health services researcher. "We are taught in medicine to
be brave and to be strong, but there should also be a time and place for emotional
expression, and perhaps even for crying. Doctors, nurses and other members of the
healthcare team must be steady sources of support for patient. But when the patient
encounter is over, at the end of the day, the doctor or nurse or social worker or clerk
needs to be able to process everything they have seen and experienced. We need to support
people who work with the sickest of the sick," she said.
Last step leading to blood cell
formation elucidated
These new insights represent an important
contribution to future clinical therapeutic approaches. The study was published in the
prestigious science journal Nature and will be a central topic of the international
symposium on the molecular mechanisms of hematopoiesis, which will take place in Munich
from April 2nd to 4th. The findings on the molecular mechanisms of blood formation
(hematopoiesis) will be presented in Munich at the international symposium "Molecular
Mechanisms of Normal and Malignant Hematopoiesis" from April 2nd to 4th. A question
that has puzzled researchers for decades could now be solved: How are the first blood
cells generated in the embryo? In particular, Dr. Timm Schroeder, research group leader at
the Institute of Stem Cell Research of Helmholtz Zentrum Muenchen and his team found out
that a special type of endothelial cells exists that can transform themselves into blood
cells. Endothelial cells line the interior surface of blood vessels. Dr. Timm Schroeder
explained "It is extremely difficult to investigate the blood cell generation
process. It occurs only very briefly, hidden from view in the embryo within the mother's
uterus." The scientists first had to create the technical means to continually
observe the transformation process of endothelial cells into blood cells on the
single-cell level over a longer period of time. Dr. Schroeder and his colleagues developed
novel bioimaging techniques with which the behavior of large numbers of individual cells
can be recorded and tracked. They combined optimized microscopy, incubation and imaging
technology as well as novel software programs to track individual cells in time-lapse
videos with sophisticated cell purification and cell culture techniques. Thus, the
scientists could observe the behavior of many differentiating mesodermal cells over a
period of up to one week. By carefully analyzing thousands of cells and the molecules
expressed by them, Dr. Schroeder and PhD student Hanna Eilken were able to detect several
very rare endothelial cells that indeed transformed themselves into blood cells.
Blood protein may hold key to
stopping tumor growth in cancer patients
A recent discovery by researchers at Wake
Forest University School of Medicine could clear the way for a new drug that inhibits
tumor growth in cancer patients and could potentially help in the healing of wounds.
The discovery stems from a study, recently published in the Proceedings of the National
Academy of Sciences of the United States of America, in which researchers looked at
angiogenesis – the body's formation of new blood vessels from existing blood vessels
– and how some blood proteins are involved in that process and affect blood vessel
growth. Researchers found that a protein called ferritin binds to and cripples the ability
of another blood protein, called HKa, to shut down blood vessel growth. Because new blood
vessels supply a steady stream of nutrients and oxygen that are essential for tumor
growth, researchers found that the binding of the two proteins actually assists in new
blood vessel formation by removing HKa's influence and therefore promotes tumor growth.
The finding led researchers to the hypothesis that if they can somehow prevent the binding
of ferritin and HKa, it will allow HKa to prevent new blood vessel growth and therefore
block the growth of tumors. The finding also has possible implications for wound care. In
order to heal, wounds need blood vessel growth. It is therefore possible that by
increasing the binding of ferritin to HKa, one could increase the rate at which a serious
wound heals.
Babies born to women with anxiety
or depression are more likely to sleep poorly
A study in the April 1 issue of the journal
SLEEP suggests that babies are more likely to have night wakings at both 6 months and 12
months of age if they are born to women who suffered from anxiety or depression prior to
the pregnancy. Results indicate that preconceptional psychological distress – anxiety
or depression - was a strong predictor of infant night waking, independent of the effects
of postnatal depression, bedroom sharing and other confounding factors. Significant
psychological distress prior to conception was associated with a 23-percent increased risk
of infant night wakings at 6 months of age and a 22-percent increased risk at 12 months of
age. According to the authors, frequent, disruptive night wakings in the latter period of
the first year of life are clinically relevant because they predict sleep problems at
three years of age, which in turn are associated with behavioral problems. During early
childhood development, poor sleep quality also may affect learning abilities. Infant night
wakings also disrupt a mother's sleep, which predicts maternal mood, stress and fatigue.
The study involved 874 women between 20 and 34 years of age in the city of Southampton,
U.K. Before becoming pregnant the women completed the General Health Questionnaire, a
12-question screening instrument that detects depression and anxiety disorders.
Twenty-nine percent of the women were classified as having significant psychological
distress. When their baby was 6 months and 12 months of age, the women reported how often
their child had awakened on average between the hours of midnight and 6 a.m. each night
during the last two weeks. The percentage of children who woke at least once each night
was higher among women with psychological distress prior to the pregnancy, both at 6
months of age (52 percent vs. 43 percent) and 12 months of age (46 percent vs. 36
percent). According to the authors, untreated infant sleep problems can become chronic,
with implications for the mental health and well-being of both the child and the mother.
The difficulties of mothers who are already vulnerable to anxiety and depression will be
exacerbated if they also are deprived of sleep. The authors conclude that recognizing and
treating psychological distress before, during and after pregnancy may promote improved
infant sleep.
Maternal smoking may alter the
arousal process of infants, increasing their risk for SIDS
A study in the April 1 issue of the journal
SLEEP shows that maternal smoking is associated with an impaired infant arousal process
that may increase the risk for sudden infant death syndrome (SIDS). The authors suggest
that maternal smoking has replaced stomach sleeping as the greatest modifiable risk factor
for SIDS. Results show that the progression from sub-cortical activation to cortical
arousal was depressed in smoke-exposed infants, who had lower proportions of full cortical
arousals from sleep and higher proportions of sub-cortical activations than infants born
to non-smoking mothers. The study also indicates that there is a dose-dependent
relationship between cortical activation proportions and levels of infant urinary
cotinine, a nicotine metabolite. Cortical arousals were lowest in babies with higher
levels of smoke exposure.
According to senior investigator Rosemary Horne, PhD, scientific director of the Ritchie
Centre for Baby Health Research at Monash University in Melbourne, Australia, decreased
cortical arousals from sleep have been observed in victims of SIDS prior to death.
"Our study suggests that maternal smoking can impair the arousal pathways of
seemingly normal infants, which may explain their increased risk for SIDS," said
Horne.
According to the authors, SIDS is the third-leading cause of infant mortality in the U.S.
Although the exact cause is unknown, research suggests that an impairment of the arousal
process from sleep in response to a life-threatening situation is involved. Autopsies of
SIDS victims have revealed brainstem abnormalities in key areas that are required for
arousal and cardiorespiratory control. The study involved 12 healthy, full-term infants
born to mothers who smoked an average of 15 cigarettes per day. Their arousal responses
during daytime sleep were monitored and compared with that of 13 healthy infants who were
born to nonsmoking mothers.
Team identifies a molecular switch
linking infectious disease and depression
Researchers at the University of Illinois
report that IDO, an enzyme found throughout the body and long suspected of playing a role
in depression, is in fact essential to the onset of depressive symptoms sparked by chronic
inflammation. Their study, just published online in the Journal of Immunology, is the
first to identify IDO (indoleamine 2,3 dioxygenase) as a molecular switch that induces
depressive symptoms in some cases of chronic inflammation. Doctors have known for decades
that patients with chronic inflammation, such as that linked to coronary heart disease or
rheumatoid arthritis, are more likely than others to become depressed. Some
pro-inflammatory drugs, such as interferon-alpha, which is used to treat Hepatitis C and a
cancer known as malignant melanoma, also induce symptoms of depression in a significant
number of patients. In the new study, mice were exposed to Bacille Calmette–Guérin
(BCG), a vaccine used in many parts of the world to prevent tuberculosis. BCG produces
low-grade, chronic inflammation in mice, which can be detected by measuring levels of
certain immune system proteins, called inflammatory cytokines, in the blood and brain.
Mice exposed to BCG display the normal symptoms of illness (lack of appetite, reduced
activity), but after these symptoms fade the mice continue to exhibit depressive-like
behaviors that can be reversed with antidepressants, said animal sciences and pathology
professors Keith Kelley and Robert Dantzer, who led the study. Even after they recover
from their sickness, the BCG-infected mice are much more passive than non-infected mice
when in an inescapable situation. When placed in a bucket of water for a few minutes, for
example, they struggle less to escape and spend more time floating passively, the
researchers report. "The mice that we're calling depressed give up more quickly.
While physically able, the mice quit trying to escape," said animal sciences
professor Jason O'Connor, first author on the study. "But if you give them
anti-depressants, the depressive-like behavior goes away," Kelley said. "So the
next question is, how can this be?" Dantzer said. "What is the biological
molecular switch which makes them go from sickness to depression?" The researchers
knew that infection causes immune cells to produce cytokines, signaling proteins that help
the body fight infection. These proteins also activate IDO in the body and brain. IDO
degrades the amino acid tryptophan, producing metabolites that affect animal and human
behavior. Previous studies have found a strong correlation between an increase in these
metabolites and the depressive symptoms seen in some patients.An analysis of gene
regulation in the mouse brains showed that exposure to BCG increased expression of IDO and
two cytokines known to induce IDO: tumor necrosis factor-alpha and interferon-gamma.
Because IDO degrades tryptophan, which is the precursor of serotonin, a brain chemical
known to positively influence mood, scientists have hypothesized that the depression seen
in patients with inflammatory disease was due to a decrease in serotonin in the brain. But
a check of serotonin in the brains of mice with depressive-like behavior showed otherwise,
Dantzer said. "The brain is able to compensate for the decrease in tryptophan,"
he said.
A mother's criticism causes
distinctive neural activity among formerly depressed
Formerly depressed women show patterns of
brain activity when they are criticized by their mothers that are distinctly different
from the patterns shown by never depressed controls, according to a new study from Harvard
University. The participants reported being completely well and fully recovered, yet their
neural activity resembled that which has been observed in depressed individuals in other
studies. The study, which appears in the current issue of the journal Psychiatry Research:
Neuroimaging, was led by Jill M. Hooley, professor of psychology in the Faculty of Arts
and Sciences at Harvard. Hooley's co-authors were Holly Parker, also of Harvard, and Staci
Gruber, Julien Guillaumot, Jadwiga Rogowska and Deborah Yurgelun-Todd of McLean Hospital
in Belmont, Mass. "We found that even though our formerly depressed participants were
fully well, had no symptoms, and felt fine, different things were happening in their
brains when they were exposed to personal criticism," says Hooley. "What's
interesting to us about these findings is that although these women were fully recovered,
at the level of the brain they were not back to normal." The study included 23 female
participants, 12 of whom had no history of depression or any other mental illness and 11
of whom had previously experienced one or more depressive episodes, but had reported no
symptoms for an average of 20 months. To an observer, both the control group and the
formerly depressed appeared completely healthy. While inside an fMRI scanner, the
participants listened to 30-second audio recordings of remarks from their mother. Some
comments were praising, some were critical and others were neutral in content. The
comments were previously recorded over the telephone with the permission of the mothers.
The participants were also asked to rate their mood on a scale from one to five after
hearing the different kinds of remarks.
Blood test for brain injuries gains
momentum
A blood test that can help predict the
seriousness of a head injury and detect the status of the blood-brain barrier is a step
closer to reality, according to two recently published studies involving University of
Rochester Medical Center researchers. News stories about tragic head injuries – from
the death of actress Natasha Richardson to brain-injured Iraq war soldiers and young
athletes – certainly underscore the need for a simpler, faster, accurate screening
tool, said brain injury expert Jeffrey Bazarian, M.D., M.P.H., associate professor of
Emergency Medicine, Neurology and Neurosurgery at URMC, and a co-author on both studies.
The S-100B blood test recently cleared a significant hurdle when a panel of national
experts, including Bazarian, agreed for the first time that it could be a useful tool for
patients with a mild injury, allowing them to safely avoid a CT scan. Previous studies
have shown the S-100B serum protein biomarker to increase rapidly after an injury. If
measured within four hours of the injury, the S-100B test accurately predicts which head
injury patients will have a traumatic abnormality such as hemorrhage or skull fracture on
a head CT scan. It takes about 20 minutes to get results and could spare many patients
unnecessary radiation exposure.
Physicians at six Emergency Departments in upstate New York, including the ED at Strong
Memorial Hospital in Rochester, this year will continue to study the accuracy of the test
among 1,500 patients. Scientists plan to use the data to apply for U.S. Food and Drug
Administration approval. "The S-100B blood test is an important part of the tool set
we need to improve our treatment of patients with brain injuries," Bazarian said.
"It's not the ultimate diagnostic test, but it may make things easier for patients,
and it will help doctors sort through difficult clinical decisions." The test is used
routinely in 16 European countries as a screening device. If a person falls and gets a
head injury in Munich, Germany, during Oktoberfest, for example, a neurosurgeon is on duty
within 500 meters of the beer tent, ready to administer the blood test, Bazarian said.
New insights into how brain
responds to viral infection
Scientists at Columbia University Mailman
School of Public Health have discovered that astrocytes, supportive cells in the brain
that are not derived from an immune cell lineage, respond to a molecule that mimics a
viral infection using cellular machinery similar to that used by classical immune cells in
the blood. While scientists have been aware of the capacity of astrocytes to trigger an
innate immune response when encountering a foreign agent, this work provides a new
understanding of the complex mechanisms responsible for induction and regulation of
inflammation in the brain and has significant implications for both the diagnosis and
treatment of brain infections. The study is published as the cover article in the April
2009 issue of The FASEB Journal (http://www.fasebj.org). In the course of trying to
contain and neutralize a virus that has breached the protective barrier of the central
nervous system, immune mediators secreted by astrocytes may injure other cells and tissues
in the vicinity and cause additional life-threatening inflammation.
By defining the nature of inflammatory responses by brain astrocytes, this study has
implications for both the diagnosis of chronic infections of the central nervous system,
as well as the treatment of acute and chronic brain infections. Viral infections of the
brain are associated with extremely high morbidity and mortality; in most cases, the
specific microbial cause is unknown. Even when a viral cause is clear, the specific
antiviral tools at our disposal remain limited. This work provides a means for
implementation of a more general therapeutic approach to viral brain infections that may
be effective across a wide range of viruses, or even where a virus is suspected but the
offending agent cannot be identified."Studies such as this take us one step closer to
understanding both the risk and benefit associated with antiviral immune response and may
lead to new treatment strategies," said W. Ian Lipkin, MD, senior author of the
paper, director of the Mailman School of Public Health's Center for Infection and
Immunity, John Snow Professor of Epidemiology, and professor of Neurology and Pathology.
The researchers compared two methods of exposing a cell to this virus-like
challenge—one from outside the cell and the other by direct delivery into the cell's
cytoplasm. By culturing the supportive cells known as astrocytes obtained from the brains
of newborn mice and exposing them to a virus-like molecule (called Poly I:C) from the
outside and the inside, the scientists were able to show for the first time the
differences between extracellular and intracellular immune response in these supportive
brain cells.
Taking cues - Sometimes
environmental cues can activate thrifty behavior
Consumers are constantly bombarded with
subtle and even subconscious cues from their environment. A new study in the Journal of
Consumer Research examines whether these cues activate goals that affect behavior in the
long term or momentary desires that fade away.Authors Aner Sela and Baba Shiv (both
Stanford Graduate School of Business) investigated the difference between goals that
influence behavior and semantic activation, which has no lingering effect on
behavior."Passing mindlessly by a discount store on the way to the mall might
activate the goal of being frugal, which can sustain for a relatively long duration and
influence subsequent purchases at the mall," explain the authors.
"Alternatively, the same discount store may simply bring to mind the semantic notion
of frugality, without actually activating the lingering motivation to behave
frugally."The difference between the two outcomes, the authors believe, depends on
the degree to which the primed concept (like frugality) is perceived as discrepant from
the consumer's self-concept. In other words, a person who does not see himself as frugal
who is exposed to a prime is more likely to activate a goal of frugality and to pursue
that goal until he feels he has fulfilled it. But someone who already believes she is
frugal is more likely to respond to the prime in a short-term fashion.In the experiments,
the authors asked a large group of university students to rate the extent to which they
saw themselves as physically fit. Then the authors exposed the participants to quick
flashes of words related to physical fitness (primes) without participants being aware of
the exposure. Finally the participants were asked to select and drink one of two energy
beverages: They were told one boosted mental acuity and the other boosted fitness.
What's in your water? Disinfectants
create toxic by-products
Although perhaps the greatest public health
achievement of the 20th century was the disinfection of water, a recent study now shows
that the chemicals used to purify the water we drink and use in swimming pools react with
organic material in the water yielding toxic consequences. University of Illinois
geneticist Michael Plewa said that disinfection by-products (DBPs) in water are the
unintended consequence of water purification. "The reason that you and I can go to a
drinking fountain and not be fearful of getting cholera is because we disinfect water in
the United States," he said. "But the process of disinfecting water with
chlorine and chloramines and other types of disinfectants generates a class of compounds
in the water that are called disinfection by-products. The disinfectant reacts with the
organic material in the water and generates hundreds of different compounds. Some of these
are toxic, some can cause birth defects, some are genotoxic, which damage DNA, and some we
know are also carcinogenic." The 10-year study began with an EPA grant to develop
mammalian cell lines that would be used specifically to analyze the ability of these
compounds to kill cells, or cytotoxicity, and the ability of these emerging disinfection
by-products to cause genomic DNA damage. "Our lab has assembled the largest
toxicological data base on these emerging new DBPs. And from them we've made two
fundamental discoveries that hopefully will aid the U.S. EPA in their regulatory
decisions. The two discoveries are somewhat surprising," Plewa said. The first
discovery involves iodine-containing DBPs. "You get iodine primarily from sea water
or underground aquifers that perhaps were associated with an ancient sea bed at one time.
If there is high bromine and iodine in that water, when you disinfect these waters, you
can generate the chemical conditions necessary to produce DBPs that have iodine atoms
attached. And these are much more toxic and genotoxic than the regulated DBPs that
currently EPA uses," he said. Plewa said that the second discovery concerns
nitrogen-containing DBPs. "Disinfectant by-products that have a nitrogen atom
incorporated into the structure are far more toxic and genotoxic, and some even
carcinogenic, than those DBPs that don't have nitrogen. And there are no
nitrogen-containing DBPs that are currently regulated." In addition to drinking water
DBPs, Plewa said that swimming pools and hot tubs are DBP reactors. "You've got all
of this organic material called 'people' -- and people sweat and use sunscreen and wear
cosmetics that come off in the water. People may urinate in a public pool. Hair falls into
the water and then this water is chlorinated. But the water is recycled again and again so
the levels of DBPs can be ten-fold higher than what you have in drinking water."
Plewa said that studies were showing higher levels of bladder cancer and asthma in people
who do a lot of swimming - professional swimmers as well as athletic swimmers. These
individuals have greater and longer exposure to toxic chemicals which are absorbed through
the skin and inhaled. "The big concern that we have is babies in public pools because
young children and especially babies are much more susceptible to DNA damage in agents
because their bodies are growing and they're replicating DNA like crazy," he said.
Childhood abuse associated with
onset of psychosis in women
Researchers at the Institute of Psychiatry,
King's College London have published new research which indicates that women with severe
mental illness are more likely to have been abused in childhood that the general
population. But the same association has not been found in men. The researchers believe
their findings point to differences in the way boys and girls respond to traumatic and
upsetting experiences. The paper which is published in the April issue of the British
Journal of Psychiatry compared two groups of adults with all the participants were aged
between 16 and 64, and lived in either south-east London or Nottingham.
Those in the first group had experienced psychotic symptoms, such as hallucinations or
delusions and received treatment for depression, mania or schizophrenia. Those in the
second group had no mental health problems, and acted as a control sample. Both groups
were asked whether they experienced physical or sexual abuse during their childhood. Women
with psychosis were twice as likely to report either physical or sexual abuse compared to
healthy women. But no such association was found in men. The researchers suggest that one
explanation for this is that girls are more likely to 'internalise' difficulties than
boys. In other words, girls who are abused may distance themselves from other people, and
become overly suspicious of other people's behaviour. This may put them at greater risk of
psychotic symptoms in the future, such as paranoid delusions. In contrast, boys may be
more likely to 'act out' following physical abuse and potentially be at greater risk for
antisocial behaviour.
Bad mix of bacterial remnants and
genetics leads to arthritis
Here's another reason to hate leftovers. A
research study appearing in the April 2009 issue of the Journal of Leukocyte Biology
(http://www.jleukbio.org) sheds light on one cause of arthritis: bacteria. In the study,
scientists from the United States and The Netherlands show that a specific gene called
NOD2 triggers arthritis or makes it worse when leftover remnants of bacteria cell walls,
called muramyl dipeptide or MDP, are present. This discovery offers an important first
step toward new treatments to prevent or lessen the symptoms of inflammatory
arthritis."Despite recent advances in the treatment of arthritis, none target its
cause," said Michael Davey, Associate Chief of Staff for Research at the Portland
Oregon Veteran's Affairs Medical Center and one of the researchers involved in the study.
"Our work with MDP and NOD2 is a step toward understanding the root cause of
arthritis which one day may allow certain forms of arthritis to be prevented
altogether." Davey and colleagues made this discovery through experiments using two
groups of mice, one group was normal and the other had been genetically modified so that
their NOD2 gene was deactivated (commonly referred to as "knocked out"). Then
they administered MDP to the joints of mice in each group, and unlike the normal group of
mice, the mice with the deactivated NOD2 gene did not experience signs of arthritis. This
may also be an important advance in the understanding and treatment of Blau Syndrome, a
rare genetic disease characterized by granulomatous arthritis (arthritis caused by
bacteria), uveitis (inflammation in the middle layer of the eye), skin rash and cranial
neuropathy (a disorder affecting nerves that control sight, eye movement, hearing, and
taste). "Now that we know that bacterial products can activate this NOD2 pathway and
that this signal contributes to arthritis," said John Wherry, Ph.D., Deputy Editor of
the Journal of Leukocyte Biology, "the next step is to find treatments that either
rid the body of this inflammatory signal or mask it. Either way, the net effect would be
the same: people would be spared from a very crippling disease. "
