News 05 march 2009
Immune Reaction to Metal Debris
Leads to Early Failure of Joint Implants
Researchers at Rush University Medical
Center have identified a key immunological defense reaction to the metals in joint
replacement devices, leading to loosening of the components and early failure. The study,
funded by the National Institutes of Health, won the annual William H. Harris, MD Award
for scientific merit from the Orthopaedic Research Society. Currently posted online, it is
expected to be published in the June issue of the Journal of Orthopaedic Research. Over
600,000 total joint replacements are performed in the United States each year. The vast
majority are successful and last well over 10 years. But in up to 10 percent of patients,
the metal components loosen, requiring the patient to undergo a second surgery. The
loosening is often caused by localized inflammation, an immune reaction to tiny particles
of debris from the components themselves as they rub against one another. No infection is
involved. “As soon as joint replacement devices are implanted, they begin to corrode
and wear away, releasing particles and ions that ultimately signal danger to the
body’s immune system,” said Nadim Hallab, associate professor at Rush University
Medical Center and the study author. There are two different types of inflammatory
pathways: one that reacts to foreign bodies like bacteria and viruses, which cause an
infection, and another that reacts to “sterile” or non-living danger signals,
including ultraviolet light and oxidative stress.
This is the first time that researchers have shown that debris and ions from implants
trigger this danger-signaling pathway.
How Shift Work Can Adversely Affect
Health
Christos Mantzoros, MD, is Clinical
Research Overseer of the Department of Endocrinology, Diabetes and Metabolism at Beth
Israel Deaconess Medical Center (BIDMC). Over the past 14 years, Mantzoros has studied the
leptin hormone, which controls appetite and satiety, publishing more than 110 original
papers and several book chapters on the subject. In an article in the March 2 Advance
On-line issue of the Proceedings of the National Academy of Sciences (PNAS), Mantzoros,
together with colleagues from the Sleep Disorders Research Program at Brigham and
Women’s Hospital, describe new findings that help explain why night-shift workers are
at increased risk of metabolic and cardiac disease, including obesity, diabetes and
hypertension. And, among their key discoveries, is the important role that leptin plays.
Protein structure determined in
living cells
The function of a protein is determined
both by its structure and by its interaction partners in the cell. Until now, proteins had
to be isolated for analyzing them. An international team of researchers from Tokyo
Metropolitan University, Goethe University, and the Frankfurt Institute for Advanced
Studies (FIAS) has, for the first time, determined the structure of a protein in its
natural environment, the living cell. Using nuclear magnetic resonance (NMR) spectroscopy,
the researchers solved the structure of a protein within the bacterium Escherichia coli.
"We have reached an important goal of molecular biology", says Prof. Peter
Güntert from the Goethe University's Biomolecular Magnetic Resonance Center. (BMRZ) of
The research results will be published by the scientific journal Nature on March 5, 2009.
Conventionally, proteins are extracted from the cell, purified, and analyzed in
single crystals or in solution. NMR spectroscopy detects signals from the nuclei of
hydrogen atoms that are ubiquitous in organic molecules. Measurements in the living cell
are challenging because it is difficult to distinguish between the protein of interest and
the many other proteins in the cytoplasm. The Japanese researchers around Prof. Yutaka Ito
solved this problem by introducing the gene of a putative heavy-metal-binding protein into
the model system Escherichia coli, where the protein was in high concentration. The
success of the measurements relies on the method of "in-cell" NMR spectroscopy
that was developed a few years ago by Prof. Volker Dötsch from BMRZ at Goethe University.
Dötsch was able to attribute signals from living cells to specific proteins that he had
labeled with the stable nitrogen isotope N-15. However, it was not possible to calculate a
three-dimensional structure. "About two days of measurement time are required to
measure a multidimensional NMR spectrum", says Peter Güntert. "Unfortunately,
the cells survive for only a 5-6 hours without supply of oxygen and nutrients. Güntert
and his colleagues compensated for the concomitant drastic reduction of the measurement
time by computational reconstruction of the complete spectrum. Then, they calculated a
detailed three-dimensional structure of the protein within E. coli cells using software
that was developed in their research group.
Magnetic nanoparticles navigate
therapeutic genes through the body
Health professionals send genes and healthy
cells on their way through the bloodstream so that they can, for example, repair tissue
damage to arteries. But do they reach their destination in sufficient quantities?
Scientists of the PTB have developed a highly sensitive measuring method with which the
efficiency of this therapy can be investigated: Small magnetic particles which are
situated on the planted gene or on the planted cell can with the aid of an external
magnetic field be specifically directed to the location of the damage. There the
researchers determine, accurate to the picogram per cell, the quantity of the magnetic
material – and thus also the quantity of the therapeutically effective genes or
cells. In a joint study with the University of Bonn it became clear: By means of the
magnetic method it is possible to dramatically increase the efficiency of the gene
transfer in comparison to the non-magnetic method. Magnetic nanoparticles can support or
even enable gene transfer under clinically relevant experimental conditions. For the
transduction of human cells, gene carriers were coupled to magnetic nanoparticles and
dragged into the cells by magnetic field gradients. The efficiency of magnetic
transduction turned out to be much higher than the nonmagnetic procedure. An additional
welcome side effect is the "magnetization" of the cells after the incorporation
of nanoparticles. This may enable the targeted transport of the cells to regions of
interest.
Stem cell breakthrough gives new
hope to sufferers of muscle-wasting diseases
An experimental procedure that dramatically
strengthens stem cells' ability to regenerate damaged tissue could offer new hope to
sufferers of muscle-wasting diseases such as myopathy and muscular dystrophy, according to
researchers from the University of New South Wales (UNSW). The world-first procedure has
been successfully used to regrow muscles in a mouse model, but it could be applied to all
tissue-based illnesses in humans such as in the liver, pancreas or brain, the researchers
say. The research team, which is based at UNSW and formerly from Sydney's Westmead
Children's Hospital, adapted a technique currently being trialled in bone marrow
transplantation. Adult stem cells are given a gene that makes them resistant to
chemotherapy, which is used to clean out damaged cells and allow the new stem cells to
take hold. A paper detailing the breakthrough appears in the prestigious journal Stem
Cells this week. The ability of adult stem cells to regenerate whole tissues opens up a
world of new possibilities for many human diseases, according to the lead authors of the
paper, Professor Peter Gunning, Professor Edna Hardeman and Dr Antonio Lee, from UNSW's
School of Medical Sciences. "The beauty of this technique is that chemotherapy makes
space for stem cells coming into muscle and also gives the stem cells an advantage over
the locals. It's the first strategy that gives the good guys the edge in the battle to
cure sick tissues," Professor Gunning said. "What has been the realm of science
fiction is looking more and more like the medicine of the future," he said.
Immune cells from patients with
rheumatoid arthritis have prematurely aged chromosomes
Telomeres, structures that cap the ends of
cells' chromosomes, grow shorter with each round of cell division unless a specialized
enzyme replenishes them. Maintaining telomeres is thought to be important for healthy
aging and cancer prevention. By this measure, T cells, or white blood cells, from patients
with the autoimmune disease rheumatoid arthritis are worn out and prematurely aged,
scientists at Emory University School of Medicine have discovered. Compared with cells
from healthy people, T cells from patients with rheumatoid arthritis have trouble turning
on the enzyme that replenishes telomeres, they found. Reversing this defect could possibly
help people prone to the disease maintain a balanced immune system.
The results are published online this week in Proceedings of the National Academy of
Sciences. In rheumatoid arthritis, T cells are chronically over-stimulated, invading the
tissue of the joints and causing painful inflammation. This derangement can be seen as a
result of the loss of the immune system's ability to discriminate friend from foe, says
senior author Cornelia Weyand, MD, PhD, co-director of the Kathleen B. and Mason I.
Lowance Center for Human Immunology at Emory University. In childhood, new T cells are
continually produced in the thymus, she says. But after about age 40, the thymus
"involutes" – or shrinks and ceases to function. After that, the immune
system has to make do with the pool of T cells it already has.
"What we see in rheumatoid arthritis is an aged and more restricted T cell
repertoire," she says. "This biases the immune system toward autoimmunity."
Weyand, postdoctoral fellow Hiroshi Fujii, MD, PhD, and their colleagues were interested
in mechanisms of T cells' premature aging, because scientists had previously observed that
in rheumatoid arthritis, T cells tend to shift the molecules on their surface and function
differently. They found the answer in telomerase, the enzyme that renews telomeres and is
necessary to prevent loss of genetic information after repeated cell division.
Study finds injectable birth control causes
significant weight gain and changes in body mass
Women using depot medroxyprogesterone
acetate (DMPA), commonly known as the birth control shot, gained an average of 11 pounds
and increased their body fat by 3.4 percent over three years, according to researchers at
the University of Texas Medical Branch (UTMB). However, women who switched to nonhormonal
contraception began to slowly lose the weight and fat mass they gained – nearly four
pounds over two years, while those who used oral contraception after the shots gained an
average of four additional pounds in the same time span. The amount of weight gain was
dependent on the length of time DMPA was used, as the rate of weight gain slowed over
time. The study, which appears in the March 4 issue of the American Journal of Obstetrics
and Gynecology, is one of the most comprehensive studies of its kind. DMPA is an injected
contraceptive administered to patients every three months. More than two million American
women use DMPA, including approximately 400,000 teens. DMPA is relatively inexpensive
compared to some other forms of birth control, has a low failure rate and doesn't need to
be administered daily, which contributes to the contraceptive's popularity. "Women
and their doctors should factor in this new data when choosing the most appropriate birth
control method," said lead author Abbey Berenson, M.D., professor in the Department
of Obstetrics and Gynecology and director of the Center for Interdisciplinary Research in
Women's Health at UTMB. "One concern is DMPA's link to increased abdominal fat, a
known component of metabolic syndrome, which increases the risk of cardiovascular disease,
stroke and diabetes," said Berenson. The study followed 703 women in two age
categories, 16- to 24-years-old, and 25- to 33-years-old, using DMPA, oral (desogestrel)
or nonhormonal (bilateral tubal ligation, condom or abstinence) contraception for three
years. DMPA users who discontinued this method and selected another form of birth control
were followed for up to two additional years. Throughout the course of the study,
researchers compared changes in body weight and composition and took into account the
influence of age, race, caloric intake and exercise, among other factors.
When researchers compared all three groups, DMPA users were more than twice as likely as
women using nonhormonal or oral birth control to become obese over the next three years.
"The findings are worrisome; however, more research is needed to determine if DMPA
use directly contributes to obesity-related conditions and puts patients' overall health
at risk," said Berenson.
While Driving, Cell Phones =
Increased Fatalities
Cell phones are a danger on the road in
more ways than one. Two new studies show that talking on the phone while traveling,
whether you’re driving or on foot, is increasing both pedestrian deaths and those of
drivers and passengers, and recommend crackdowns on cell use by both pedestrians and
drivers. The new studies, lead-authored by Rutgers University, Newark, Economics Professor
Peter D. Loeb, relate the impact of cell phones on accident fatalities to the number of
cell phones in use, showing that the current increase in deaths attributed to cell phone
use follows a period when cell phones actually helped to reduce pedestrian and traffic
fatalities. However, this reduction in fatalities disappeared once the numbers of phones
in use reached a “critical mass” of 100 million, the study found. These studies
looked at cell phone use and motor vehicle accidents from 1975 through 2002, and factored
in a number of variables, including vehicle speed, alcohol consumption, seat belt use, and
miles driven. The studies found the cell phone-fatality correlation to be true even when
weighing in factors such as speed, alcohol consumption, and seat belt use. Loeb and his
co-author determined that, at the current time, cell phone use has a “significant
adverse effect on pedestrian safety” and that “cell phones and their usage above
a critical threshold adds to motor vehicle fatalities.” In the late 1980s and part of
the 1990s, before the numbers of phones exploded, cell phone use actually had a
“life-saving effect” in pedestrian and traffic accidents, Loeb notes.
“Cell-phone users’ were able to quickly call for medical assistance when
involved in an accident. This quick medical response actually reduced the number of
traffic deaths for a time,” Loeb hypothesizes.
Researchers find brain differences
between believers and non-believers
Believing in God can help block anxiety and
minimize stress, according to new University of Toronto research that shows distinct brain
differences between believers and non-believers. In two studies led by Assistant
Psychology Professor Michael Inzlicht, participants performed a Stroop task – a
well-known test of cognitive control – while hooked up to electrodes that measured
their brain activity. Compared to non-believers, the religious participants showed
significantly less activity in the anterior cingulate cortex (ACC), a portion of the brain
that helps modify behavior by signaling when attention and control are needed, usually as
a result of some anxiety-producing event like making a mistake. The stronger their
religious zeal and the more they believed in God, the less their ACC fired in response to
their own errors, and the fewer errors they made.
"You could think of this part of the brain like a cortical alarm bell that rings when
an individual has just made a mistake or experiences uncertainty," says lead author
Inzlicht, who teaches and conducts research at the University of Toronto Scarborough.
"We found that religious people or even people who simply believe in the existence of
God show significantly less brain activity in relation to their own errors. They're much
less anxious and feel less stressed when they have made an error." These correlations
remained strong even after controlling for personality and cognitive ability, says
Inzlicht, who also found that religious participants made fewer errors on the Stroop task
than their non-believing counterparts. Their findings show religious belief has a calming
effect on its devotees, which makes them less likely to feel anxious about making errors
or facing the unknown. But Inzlicht cautions that anxiety is a "double-edged
sword" which is at times necessary and helpful.Bad behaviour may leave bad taste in
your mouth, says U of T research In everyday language, people sometimes say that immoral
behaviours "leave a bad taste in your mouth." But this may be more than a
metaphor according to new scientific evidence from the University of Toronto that shows a
link between moral disgust and more primitive forms of disgust related to poison and
disease. "Morality is often pointed to as the pinnacle of human evolution and
development," said lead author Hanah Chapman, a graduate student in the Department of
Psychology. "However, disgust is an ancient and rather primitive emotion which played
a key evolutionary role in survival. Our research shows the involvement of disgust in
morality, suggesting that moral judgment may depend as much on simple emotional processes
as on complex thought." The research was published in Science on Feb. 27. In the
study, the scientists examined facial movements when participants tasted unpleasant
liquids and looked at photographs of disgusting objects such as dirty toilets or injuries.
They compared these to their facial movements when they were subjected to unfair treatment
in a laboratory game. The U of T team found that people make similar facial movements in
response to both primitive forms of disgust and moral disgust.
Kidney disease increases the risk
of stroke in patients
Chronic kidney disease increases the risk
of stroke in patients with atrial fibrillation (AF), the most common type of heart
arrhythmia, according to a new study by Kaiser Permanente researchers in the current
online issue of Circulation. It has long been known that chronic kidney disease is a risk
factor for cardiovascular disease. This study is the first to look at whether chronic
kidney disease independently increases risk of stroke in patients with AF. AF occurs when
rapid, disorganized electrical signals in the heart's two upper chambers (the atria) cause
the heart to contract fast and irregularly, they explain. The finding is an important
addition to the evidence base because atrial fibrillation affects more than 2.2 million
Americans, particularly those 75 and older, and increases the risk of stroke nearly four
fold, according to the researchers. In this study, the researchers looked at whether
kidney disease increased the risk of ischemic stroke -- the most common kind of stroke
that occurs when an artery to the brain in blocked.
The risk of stroke varies according to several demographic and clinical characteristics
and current risk assessment strategies can be limited, according to the study's lead
author Alan S. Go MD, Director of the Comprehensive Clinical Research Unit at the Kaiser
Permanente Division of Research. "Our study suggests that kidney function may provide
an additional clue about how to best assess stroke risk and decide upon the best
prevention strategy for patients with AF," Go said.
Innappropriate drug prescriptions
wasting millions, raising health risks
A recent study in Oregon suggests that
drugs designed for treating the most severe mental illnesses are often prescribed at
inappropriately low doses and at considerable expense, for use in conditions where their
benefit has not been established.
In this case, prescription drugs that might cost as much as $20 to $25 a day were being
widely used to treat problems for which they were not FDA-approved. Some of those problems
could have been addressed with generic medications costing $1 a day, with better results
and less risk of serious side effects. This is a reflection of widespread use of
medications for "off-label" uses that have not been carefully considered or
approved by the Food and Drug Administration, researchers said, some of which are
unnecessarily raising medical costs and reducing the effectiveness of health care. The
research was done by scientists in the College of Pharmacy at Oregon State University, the
Department of Psychiatry at Columbia University, and Oregon Health and Science University.
It was published in the Journal of Clinical Psychiatry, and funded by the National
Institutes of Health. "It's legal for a physician to prescribe a medication for
something other than its FDA-approved uses, and based on good studies or clinical judgment
it may be justified," said Daniel Hartung, an assistant professor of pharmacy
practice at OSU. "However, the approved uses are usually a pretty good proxy for
real, proven effectiveness. And if in fact drugs are being used inappropriately, it not
only can be very expensive but also pose an unnecessary health risk."
Both of those problems were found in this study.
Almost half of all adolescents
suffer low back pain
A study led by Catalan researchers confirms
that 40% of adolescents have low back pain at least once a month. However, the real effect
of this pain is minimal in 90% of cases. Another important piece of information: only 35%
of adolescents have not had any type of pain in the last month. The study, carried out by
various Catalan research centres in collaboration with two Swiss hospitals, analysed the
prevalence of low back pain in Spain and examined whether this discomfort affects the
quality of life of adolescents. The results showed that 40% of young people do have pain
(over 24 hours of discomfort in the past month). The research, published in the journal,
Archives of Pediatrics & Adolescent Medicine, was conducted in Barcelona and Freiburg.
In the Swiss city the data of all adolescents between 14 and 15 years old was recorded,
while in Barcelona a representative sample of the same age range was analysed. The study
included a total of 1,470 participants. "It needs to be pointed out that the data
from Barcelona is the same as that from the city of Freiburg, which gives an idea of the
universal nature of our findings. Although both cities represent the Western world, they
are two completely different contexts", SINC was informed by Ferrán Pellisé, the
main author of the study and doctor from the Spinal Unit at the Vall d'Hebrón Hospital in
Barcelona.
