News 1 juli 2009
New MRI technique could mean fewer
breast biopsies in high-risk women
A University of Wisconsin-Madison biomedical engineer and colleagues have developed a
method that, applied in MRI scans of the breast, could spare some women with increased
breast cancer risk the pain and stress of having to endure a biopsy of a questionable lump
or lesion.The universal technology will give radiologists greater confidence in visually
classifying a lesion as malignant or benign. The American Cancer Society recommends that
women with certain breast cancer risk factors — including inherited genetic
mutations, family or personal history of breast cancer, or previous radiation therapy to
the chest — receive an annual MRI screening in addition to their yearly
mammogram.During a breast MRI, which lasts about a half hour, the technician injects a
contrast agent into a vein in the patient's arm. Over time, the contrast agent flows
throughout the body, including the breasts. Because they are growing quickly, cancerous
lesions often have immature vasculature, and the contrast agent flows in and
"leaks" out quickly. Conversely, benign lesions show more gradual in and out
flow. "The tricky ones are the ones that enhance quickly and then fall off more
slowly," says Wally Block, a UW-Madison associate professor of biomedical engineering
and medical physics. "Many of these lesions turn out to be difficult to classify and
lead to biopsy."Yet, it turns out that with the right kind of MRI scan, radiologists
can visually identify a cancerous lesion based on characteristics about its shape. For
example, breaks or interruptions in a lesion can indicate a benign fibroadenoma. Lumps
with smooth edges often are benign, while those with jagged edges can signal cancer. To
generate the kind of crisp, three-dimensional images necessary for such a diagnosis,
Block, UW-Madison radiology associate professor Fred Kelcz and graduate student Catherine
Moran are capitalizing on their unique MRI data-acquisition method. An MR image is made up
of thousands of smaller pieces of information. The conventional data-acquisition method
gathers that information slowly, and it's designed to be viewed from a single imaging
plane. "What people do now is they compromise," says Block. "They don't get
resolution in the other planes to make it a reasonable scan time. We found a way around
that."
Gene expression findings a step
toward better classification and treatment of juvenile arthritis
Scientists have discovered gene expression differences that could lead to better ways to
classify, predict outcome, and treat juvenile idiopathic arthritis (JIA). Eventually such
findings could enable doctors to target more aggressive treatment to children at risk of
more severe arthritis, while those likely to have milder disease could be spared the
stronger treatments that carry a greater risk of side effects. The researchers were
supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS), a part of the National Institutes of Health. JIA is an inflammatory and sometimes
disabling joint disease that affects an estimated 294,000 children in the United States.
At present, making a diagnosis of JIA is imprecise and based largely on the presence of
joint inflammation persisting for at least six weeks, for which no other cause can be
determined, says Robert A. Colbert, M.D., Ph.D., chief of the NIAMS Pediatric
Translational Research Branch. Based on the number of joints involved and other clinical
features (fever and rash, for example), doctors classify patients into one of four or five
major subtypes of JIA, which helps them predict a patient's most likely outcome and guide
appropriate treatments. "But, recent research suggests there is more variability in
JIA than the four or five major subtypes we currently recognize," Dr. Colbert says.
In the first of two such NIAMS-supported studies to be published in the July issue of
Arthritis & Rheumatism, scientists led by Michael Barnes, Ph.D., of Cincinnati
Children's Hospital Medical Center used a large data set to compare a number of children
newly diagnosed with one of four major subtypes of JIA – persistent oligoarthritis
(affecting four or fewer joints), polyarthritis (affecting five or more joints), systemic
arthritis (with fever and rash and inflammation throughout the body) and
enthesitis-related arthritis (affecting the junctions between tendons and bones). Using
gene expression technology – a method by which scientists can determine the relative
levels of expression of thousands of different genes at the same time and compare a
pattern from one subject with another – the researchers looked for differences in the
children's blood samples that corresponded with the different forms of JIA. "We
analyzed gene expression patterns in blood cells and found that we could indeed
distinguish the major subtypes of JIA," says Dr. Colbert, who was a leader of this
research program at Cincinnati Children's Hospital Medical Center before coming to NIAMS.
"Many of the genes whose expression is altered function in the immune system. This
means that not only is there immune activation, but it differs depending on the subtype of
JIA that is present."
Mayo Clinic Proceedings reviews
deep brain stimulation to treat psychiatric diseases
Pioneering therapeutic trials to investigate the effectiveness of deep brain stimulation
(DBS) in hard-to-treat depression, obsessive-compulsive disorder (OCD) and Tourette's
syndrome are underway at multiple medical centers around the world, according to a review
in the June 2009 issue of Mayo Clinic Proceedings. "Deep brain stimulation has long
been seen as valuable for controlling movement disorders," according to the review,
written by Susannah Tye, Ph.D., Mark Frye, M.D., from the Mayo Clinic Department of
Psychiatry and Psychology, and Kendall Lee, M.D., Ph.D., Mayo Clinic Department of
Neurosurgery. "It now is being investigated for hard-to-treat psychiatric
disorders," according to the authors."Early results indicate the effect on
depression and obsessive compulsive disorder is beneficial, but the therapy needs further
study," Dr. Lee says. The potential for this breakthrough treatment is enormous in
reducing the toll of mental illness on patients, their families and society, according to
the review. Unlike electroshock therapy (ECT), which stimulates the entire brain, DBS
stimulates specific parts of the brain. DBS is thought to be functionally equivalent to
creating a lesion on the brain, but with the advantage of being adjustable and reversible.
"It is like implanting a pacemaker for the brain," says Dr. Lee. The patient is
awake during deep brain stimulation surgery while a neurosurgeon implants the electrodes.
Patients are able to give immediate feedback. Additionally, patients do not feel any pain
during the implantation procedure since the brain is without pain receptors. In the
developed world, major depression is second only to cardiovascular disease in premature
mortality and time lived with disability according to the review. In persons aged 15 to 44
years, depression is the most disabling medical illness in the United States. The
prevalence of major depression, known to be a chronic and relapsing illness, is
approximately 17 percent, affecting almost 1 in 5 persons.
First Single-incision Total
Colectomy Performed at Mayo Clinic
A 32-year-old woman from Maricopa, Ariz., who was at risk for colon cancer, is believed to
be the first patient in the U.S. to undergo single-incision total colectomy — an
operation in which in the entire colon is removed. Single-incision surgery is unique in
that a single, small, three-centimeter incision is made around the navel to allow
instruments to be placed within to extract the colon. In this case, it was the only
incision made for what was a complex surgery in which the right colon, transverse colon,
descending and sigmoid colon were removed, and the patient's small bowel was joined
directly to the rectum. In traditional laparoscopic colectomy, four or five small
incisions are required to perform the operation and remove the colon.
Second gene linked to familial
testicular cancer
Specific variations or mutations in a particular can gene raise a man's risk of familial,
or inherited, testicular germ-cell cancer, the most common form of this disease, according
to new research by scientists at the National Institutes of Health. This is only the
second gene to be identified that affects the risk of familial testicular cancer, and the
first gene in a key biochemical pathway. The study appears in the July 2009 Cancer
Research. Researchers have suspected for years that heredity plays a role in some patients
with testicular germ-cell cancer, although attempts to identify a single gene with very
strong effects have been unsuccessful thus far. Scientists currently believe that multiple
genes with weaker individual effects--but acting together--probably influence an
individual's risk of familial testicular cancer. Men with a family member who had a
testicular germ cell cancer are at three-to six-fold greater risk than other men of
developing testicular cancer. Although a family history of testicular cancer probably
accounts for less than five percent of all testicular cancers, the careful study of rare
familial cancer clusters has often led to important new understanding of the non-familial
versions of the same cancer. There will be an estimated 8,400 new cases of testicular
cancer diagnosed in 2009 with about 90 percent of them being germ-cell cancers, according
to the National Cancer Institute (NCI). "This study contributes to our understanding
of why testicular germ cell cancer appears to run in families," said Raynard Kington,
M.D., Acting NIH Director. "The findings may also lead to new ways to identify men at
high risk, as well as more effective ways to prevent and treat testicular germ cell
cancer." The key pathway in this disease is the cyclic AMP pathway, which regulates
how cells respond to such signals as hormones. Drugs that affect the cyclic AMP pathway
are widely available, and, in theory, could affect progression of testicular cancer. In
this study, Anelia Horvath, Ph.D., Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), performed the laboratory research and Larissa Korde,
M.D., NCI, led the clinical cancer genetics study which identified the multiple-case
testicular cancer families used for the DNA analysis. The NICHD and NCI are parts of NIH.
The researchers found that seven different mutations in the gene in question, PDE11A,
created abnormal versions of the PDE11A enzyme that slowed down the enzyme's destruction
of cyclic AMP.
New, less invasive genetic test
greatly improves pregnancy rates in older women with poor prognosis
A new test examining chromosomes in human eggs a few hours after fertilisation can
identify those that are capable of forming a healthy baby, a researcher told the 25th
annual conference of the European Society of Human Reproduction and Embryology today
(Monday 29 June). Dr. Elpida Fragouli, from the Department of Obstetrics and Gynaecology,
University of Oxford, UK, and Reprogenetics UK, said that her team's work had already
enabled seven ongoing pregnancies in a group of older women with a history of multiple
failed IVF attempts. "Out of 35 patients who had embryo transfers after the test, we
achieved a pregnancy rate of 20%, which is exceptional considering the extremely poor
prognosis of the women involved." she said. "This represents a doubling of the
usual pregnancy rate for women who fall into this category, which is otherwise, at best,
under 10% and, at worst, zero. To date, we have two live births from this group, and all
the other women who became pregnant have maintained their pregnancies. The study is
continuing, and we believe that we will achieve more pregnancies with the help of this
technology in the future." The scientists used the Comparative Genomic Hybridisation
(CGH) technique to count the chromosomes in each egg. Unlike conventional screening
strategies, using the fluorescent in situ hybridisation (FISH) method, which allows less
than half of the chromosomes of an embryonic cell to be examined, CGH enables the
evaluation of the entire chromosome complement. CGH was used to examine the fertilised
eggs by looking at polar bodies, tiny cells that are a by-product of egg development. The
chromosomes of polar bodies provide an indication of whether the corresponding egg is
normal or abnormal; if the polar bodies have the wrong number of chromosomes, so does the
egg. Looking at polar bodies is a less invasive way of obtaining information about the
chromosome content of an egg and its resulting embryo than other alternatives, such as
day-three biopsy, which take place during conventional screening strategies involving the
use of the FISH technique. The removal of the polar bodies does not adversely affect the
subsequent development of the embryo. Additionally, the results obtained after CGH
analysis of polar bodies are not affected by the presence of chromosomal mosaicism (the
presence of two populations of cells with different genotypes) and therefore may be more
accurate than conventional methods based upon screening of cells removed from embryos.
New tool finds best heart disease
and stroke treatments for patients with diabetes
Researchers from North Carolina State University and Mayo Clinic have developed a computer
model that medical doctors can use to determine the best time to begin using statin
therapy in diabetes patients to help prevent heart disease and stroke. "The research
is significant because patients with diabetes are at high risk for cardiovascular disease
and statins are the single most commonly used treatment for patients at risk of heart
disease and/or stroke," says Dr. Brian Denton, "and this model can help
determine the best course of action for individual patients based on their risk of
developing cardiovascular disease." Denton is an assistant professor in NC State's
Edward P. Fitts Department of Industrial & Systems Engineering and lead author of the
study. Statins are a key component of current cardiovascular medical treatment guidelines,
Denton says. They lower cholesterol levels and may significantly reduce the risk of heart
attack and stroke, particularly in patients that are considered to be at high risk. The
researchers developed a new mathematical model that examines various possible treatment
policies to see how they influence short-term and long-term health outcomes for patients.
The model shows how people are affected by diabetes, and how their health changes over
time as the disease advances and patients age. The new model incorporates patient-specific
data. An established risk model calculates each patient's probability of heart attack and
stroke based on risk factors, such as their cholesterol, blood pressure, etc. This overall
risk "score" is used to weigh the medical advantages of beginning statin therapy
against the financial cost of the statins.
Risk of colon cancer
Scientists discover novel mechanism that increases the risk of common colorectal cancer.
Finnish Academy Professors Lauri Aaltonen and Jussi Taipale have identified and described
a mechanism whereby a single-base change in the human genome increases the risk of
colorectal cancer. The focus in this study was on a common single-base variant occurring
in chromosome 8, which in itself causes only a slightly increased risk of cancer. However,
the risk allele is carried by 75% of people of European origin and by almost 100% of
African populations. The high frequency of the gene variant makes it a very common cause
of cancer at the population level. At the individual level, however, the variant does not
cause significant disease predisposition because that can often be considerably reduced by
lifestyle changes. Colorectal cancer is the third most common cancer worldwide and a major
cause of cancer mortality. The variant that increases the risk of colorectal cancer was
found to be located in a regulatory region, where it changes the function of a key
regulatory element important for the development of colorectal cancer. The scientists
showed that the risk allele strengthens the binding of a regulatory factor in cancer
cells, which activates pathways that are central to the development of cancer. The impacts
of this altered genetic regulation on cell division are probably mediated via the MYC
cancer gene, which is one of the best known accelerator genes in cancer. Single-base
changes are the most common type of variation found in the human genome. Genome-wide
studies of interindividual differences in common variants can be studied using DNA chip
technology, which has greatly facilitated efforts to understand the genetic basis of
multifactorial diseases. To date, scientists have identified more than 400 variants in the
human genome that are associated with an increased risk of common diseases, such as
cancer, diabetes and cardiovascular diseases. The findings of this research lend support
to the theory that human disease susceptibility is explained in part by differences in
regulatory regions of the genome, and in gene expression. A closer understanding of the
biological mechanisms involved will help to clarify the aetiology of colorectal cancer and
pave the way to more effective cancer prevention. Apart from hereditary tumor
predisposition, another area of major strength for Finnish research is gene regulation. It
was hardly surprising therefore that Aaltonen's and Taipale's research teams found each
other so easily. The research project supervised by Aaltonen and Taipale involved
molecular biologists, medical doctors and data processing researchers from Finland and the
UK. For instance, the project made use of the EEL software developed by Professor Esko
Ukkonen and his team at the CoE for Algorithmic Data Analysis.
Debate on administration of
magnesium sulfate to pregnant women to prevent cerebral palsy in preterm infant
Cerebral palsy (CP) is the most prevalent chronic childhood motor disability with an
estimated lifetime cost of nearly $1 million per individual. There is evidence that
magnesium sulfate (MgSO4) can reduce the incidence of CP for very early preterm infants.
Many thousands of pregnant women and their fetuses are exposed to MgSO4 every year in the
United States for a variety of indications, and most obstetricians are comfortable with
its use. Yet, there is still some controversy over whether magnesium sulfate is truly
protective against CP. In three articles published in the June 2009 issue of the American
Journal of Obstetrics & Gynecology, the authors shed some light on the debate.
Investigators from the Perinatology Research Branch (Division of Intramural Research),
Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the
NIH, Bethesda, and Detroit, and the Center for Molecular Medicine and Genetics, Wayne
State University, Detroit, conducted a systematic review and meta-analysis of six
randomized controlled trials involving 4796 women and 5357 infants. Writing in the
article, Dr. Roberto Romero and Dr. Agustin Conde-Agudelo concluded that "Antenatal
magnesium sulfate should be considered for use in women at high risk of delivery before 34
weeks of gestation, mainly in those with premature rupture of membranes, labor in active
phase, and planned delivery within 24 hours." They found persuasive evidence that
administration of magnesium sulfate significantly reduces the risk of cerebral palsy in
children at risk. Continuing the debate, in an article summarizing a roundtable discussion
at the 29th Annual Meeting of the Society for Maternal–Fetal Medicine, San Diego, CA,
January 30, 2009, two researchers from the Division of Maternal–Fetal Medicine,
Department of Obstetrics and Gynecology, Washington University–St. Louis,, and the
Division of Maternal–Fetal Medicine, Department of Obstetrics, Gynecology, and
Reproductive Sciences, University of California–San Francisco, enumerate the pros and
cons of magnesium sulfate use for CP prevention. In a spirited conversation, they each
talk about the available trials and observational studies and the strengths and weaknesses
of each. Participating in the roundtable, Alison G. Cahill, MD, MSCI, and Aaron B.
Caughey, MD, PhD, observe, "Despite well-designed and executed studies, the answer to
the question of whether evidence-based medicine supports the use of magnesium for
neuroprophylaxis in all preterm pregnancies remains unclear." Dwight J. Rouse, MD, of
the Center for Women's Reproductive Health, University of Alabama at Birmingham, offers
his clinical opinion on the use of MgSO4 to prevent cerebral palsy. He notes that
"three large, randomized placebo-controlled trials of antenatal magnesium sulfate
(MgSO4) for fetal neuroprotection have recently been conducted and reported. The results
of these trials provide strong support for the utilization of MgSO4 to lower the risk of
cerebral palsy among the survivors of early preterm birth. In the United States, the use
of MgSO4 for fetal neuroprotection has the potential to prevent 1000 cases of handicapping
cerebral palsy annually."
IU researchers find vibrator use to
be common, linked to sexual health
Two Indiana University studies conducted among nationally representative samples of adult
American men and women show that vibrator use during sexual interactions is common, with
use being reported by approximately 53 percent of women and 45 percent of men ages 18 to
60. Not only is vibrator use common, but the two studies also show that vibrator use is
associated with more positive sexual function and being more proactive in caring for one's
sexual health. The studies, led by researchers at the Center for Sexual Health Promotion
in IU's School of Health, Physical Education and Recreation, are the first to publish data
about vibrator use from nationally representative samples of the U.S. population. This
lack of data has existed despite a longstanding practice by many physicians and therapists
to recommend vibrator use to help treat sexual dysfunctions or to improve sexual
enjoyment. One study surveyed women. The other surveyed men. Both were published this week
by the "Journal of Sexual Medicine," a leading peer-reviewed journal in the area
of urology and sexual health. "The study about women's vibrator use affirms what many
doctors and therapists have known for decades -- that vibrator use is common, it's linked
to positive sexual function such as desire and ease of orgasm, and it's rarely associated
with any side effects," said Debby Herbenick, associate director of the Center for
Sexual Health Promotion. Michael Reece, director of the Center for Sexual Health
Promotion, said the studies are important for the contributions they make to an
understanding of the sexual behaviors and sexual health of adults in today's society.
"The study about male vibrator use is additionally important because it shows that
vibrator use is also common among men, something that has not been documented
before," Reece said. "Also, both studies help us to further understand the way
in which American consumers are turning to the marketplace for products that promote their
sexual health, and that has important economic implications."The studies are the
first to document insights into how and why people use vibrators, examine side effects and
to explore associations with sexual health behaviors, sexual enjoyment and quality of life
measures.
For Women With PCOS, Acupuncture
And Exercise May Bring Relief, Reduce Risks
Exercise and electro-acupuncture treatments can reduce sympathetic nerve activity in women
with polycystic ovarian syndrome (PCOS), according to a new study. The finding is
important because women with PCOS often have elevated sympathetic nerve activity, which
plays a role in hyperinsulinemia, insulin resistance, obesity and cardiovascular disease
The study also found that the electro-acupuncture treatments led to more regular menstrual
cycles, reduced testosterone levels and reduced waist circumference. Exercise had no
effect on the irregular or non-existent menstrual cycles that are common among women with
PCOS, nor did it reduce waist circumference. However, exercise did lead to reductions in
weight and body mass index. “The findings that low-frequency electro-acupuncture and
exercise decrease sympathetic nerve activity in women with PCOS indicates a possible
alternative non-pharmacologic approach to reduce cardiovascular risk in these patients,”
said one of the researchers, Dr. Elisabet Stener-Victorin of the University of Gothenburg,
Sweden. The findings regarding menstrual cycles and decrease in testosterone levels in the
low-frequency electro-acupuncture are also of interest, according to the researcher. The
study, “Low-frequency electro-acupuncture and physical exercise decrease high muscle
sympathetic nerve activity in polycystic ovary syndrome” was conducted by Elisabet
Stener-Victorin, Elizabeth Jedel, Per Olof Janson and Vrsa Bergmann Sverrisdottir, all of
the Sahlgrenska Academy, University of Gothenburg, Sweden and the Karolinska Institute,
Stockholm, Sweden. The study is in the online edition of the American Journal of
Physiology-Regulatory, Integrative and Comparative Physiology, published by The American
Physiological Society.
Intestinal cells surprisingly
active in pursuit of nutrition and defense
Every cell lining the small intestine bristles with thousands of tightly packed microvilli
that project into the gut lumen, forming a brush border that absorbs nutrients and
protects the body from intestinal bacteria. In the June 29, 2009 issue of the Journal of
Cell Biology (www.jcb.org), Matthew McConnell, Matthew Tyska, and colleagues now find that
microvilli extend their functional reach even further using a molecular motor to send
vesicles packed with gut enzymes out into the lumen to get a head start on breaking down
their substrates. Microvilli have traditionally been viewed as passive scaffolds that
increase the surface area of the gut wall. The apical plasma membrane tightly wraps around
each protrusive bundle of actin, providing more space for nutrient processing and
absorption. The motor protein myosin-1a (myo1a) maintains this structure by connecting the
plasma membrane to the actin filaments. In 2007, Tyska and colleagues found that myo1a
functions in isolated brush borders to actively move membrane along the length of the
microvilli, like a "membrane escalator." To their surprise, at the top of these
escalators—the tips of the microvilli—the membrane pinched off to form small
vesicles that were released into the surrounding medium. According to Tyska, when they
showed their data to gastroenterologists, they immediately asked "Why would brush
borders do that? They're wasting perfectly good apical membrane!" Tyska therefore
wanted to see if vesicle shedding was a bona fide physiological function for microvilli.
New control system of the body
discovered
It has been known for a long time that T cells can attack the body's own structures and,
if they infiltrate the CNS, cause diseases such as multiple sclerosis (MS). The T cells
damage the myelin sheath, the material that surrounds and protects the fibers of nerve
cells. This damage slows down or blocks messages between the brain and the body, leading
to various symptoms of MS such as impaired movements. The molecular analysis of damaged
tissue from patients with MS led the researchers to the B1-receptor. The data they
evaluated showed that two different pathways known to play a crucial role in the
cardiovascular area also seem to play an important role in the CNS: namely, the
renin-angiotensin-system, and the kallikrein-kinin-system, the latter of which the
researchers in Berlin put their focus on. The B1-receptor is part of the
kallikrein-kinin-system. Together with Professor Alexandre Prat from the Université de
Montréal, Montréal, Canada, and Professor Lawrence Steinman from Stanford University in
Stanford, California, USA, the researchers in Berlin detected the B1-receptor on T cells
of MS patients as well as on T cells of mice with encephalitis, an inflammation of the
brain. The disease got worse in those mice that lacked B1 on their T cells. Therefore,
using a certain substance (Sar-[D-Phe]desArg9-bradykinin), they activated the receptor in
mice which had B1 on their T cells. As a result, the entry of T cells into the CNS slowed
down and the clinical symptoms of the inflammation markedly decreased. "We have
discovered a control mechanism, which reduces inflammation caused by the immune
system" neurologist and MDC research group leader Professor Zipp explains. "It
remains to be seen if we succeed in developing a new therapy for chronic inflammation in
the CNS, such as MS, in the future."
Reading the brain without poking it
Experimental devices that read brain signals have helped paralyzed people use computers
and may let amputees control bionic limbs. But existing devices use tiny electrodes that
poke into the brain. Now, a University of Utah study shows that brain signals controlling
arm movements can be detected accurately using new microelectrodes that sit on the brain
but don't penetrate it. "The unique thing about this technology is that it provides
lots of information out of the brain without having to put the electrodes into the
brain," says Bradley Greger, an assistant professor of bioengineering and coauthor of
the study. "That lets neurosurgeons put this device under the skull but over brain
areas where it would be risky to place penetrating electrodes: areas that control speech,
memory and other cognitive functions." For example, the new array of microelectrodes
someday might be placed over the brain's speech center in patients who cannot communicate
because they are paralyzed by spinal injury, stroke, Lou Gehrig's disease or other
disorders, he adds. The electrodes would send speech signals to a computer that would
covert the thoughts to audible words.For people who have lost a limb or are paralyzed,
"this device should allow a high level of control over a prosthetic limb or computer
interface," Greger says. "It will enable amputees or people with severe
paralysis to interact with their environment using a prosthetic arm or a computer
interface that decodes signals from the brain." The study is scheduled for online
publication July 1 in the journal Neurosurgical Focus.
Singapore nanotechnology combats
fatal brain infections
Doctors may get a new arsenal for meningitis treatment and the war on drug-resistant
bacteria and fungal infections with novel peptide nanoparticles developed by scientists at
the Institute of Bioengineering and Nanotechnology (IBN) of Singapore and reported in
Nature Nanotechnology.The stable bioengineered nanoparticles devised at IBN effectively
seek out and destroy bacteria and fungal cells that could cause fatal infections and are
highly therapeutic. Major brain infections such as meningitis and encephalitis are a
leading cause of death, hearing loss, learning disability and brain damage in patients.
IBN's peptide nanoparticles, on the other hand, contain a membrane-penetrating component
that enables them to pass through the blood brain barrier to the infected areas of the
brain that require treatment. The ability of IBN's peptide nanoparticles to traverse the
blood brain barrier offers a superior alternative to existing treatments for brain
infections. The brain membrane is impenetrable to most conventional antibiotics because
the molecular structure of most drugs is too big to enter the membrane. "Our
treatment damages the structure of the pathogen and literally breaks it apart," said
Yiyan Yang, Ph.D., group leader at IBN, one of the research institutes sponsored by
Singapore's A*STAR (Agency for Science, Technology and Research). "Our oligopeptide
has a unique chemical structure that forms nanoparticles with membranepenetrating
components on their surface," Dr. Yang added. "These nanoparticles can easily
enter bacteria, yeast or fungal cells and destabilize them to cause cell death. For
example, the nanoparticles cause damage to bacteria cell walls and prevent further
bacterial growth." The IBN research team has demonstrated that these engineered
peptide nanoparticles have high antimicrobial activity and are highly effective in killing
microbes. Additionally, the peptide nanoparticles are more powerful in inhibiting the
growth of fungal infections than conventionally available anti-fungal drugs such as
fluconazole and amphotericin B.
New trigger for chronic
inflammation in rheumatoid arthritis discovered
A signal molecule made by the human body that triggers the immune system into action may
be important in rheumatoid arthritis, according to new research published today in Nature
Medicine. The authors of the study, from Imperial College London, say that if scientists
could block this signal, it may be possible to develop more effective arthritis
treatments. Rheumatoid arthritis is the most common autoimmune disease, affecting around 1
in 100 people. It causes painful and persistent swelling in the joints that can result in
damage to the bone and cartilage. Around half of all patients do not respond to one or
more of the treatments currently available, and even these can become less successful over
time. The researchers behind the new study say stopping the disease closer to the root of
the problem could be the best way to treat it, and their results suggest a new target for
therapies. When a microbe infects the body, the body responds by turning on a molecular
switch to set the immune system into action and protect the body from disease. Today's
findings show that a signal molecule called tenascin-C can trigger the same molecular
switch and also activate the immune system. High levels of tenascin-C present in joints
therefore may cause the activated immune system to attack the joint leading to the
persistent inflammation of rheumatoid arthritis. The molecular switch is called TLR4, and
is found on the surface of immune cells. Previous research has shown that mice without
TLR4 do not show chronic joint inflammation. The researchers hope scientists can develop
new treatments that target the interaction between tenascin-C and TLR4, which may help to
combat rheumatoid arthritis.Dr Kim Midwood, lead author of the study from the Kennedy
Institute of Rheumatology at Imperial College London, said: "Rheumatoid arthritis is
a debilitating and painful disease and, unfortunately, there is no cure. Furthermore,
current treatments are not effective for many patients." "We have uncovered one
way that the immune system may be triggered to attack the joints in patients with
rheumatoid arthritis. We hope our new findings can be used to develop new therapies that
interfere with tenascin-C activation of the immune system and that these will reduce the
painful inflammation that is a hallmark of this condition," added Dr Midwood.
A potent and selective anti-tumor
agent on human gastric cancer
A research article to be published on June 21, 2009 in the World Journal of
Gastroenterology addresses this question. The research team led by Professor Yan Li from
Shengjing Hospital of China Medical University studied the growth inhibitory effects of
Alisol B acetat and determined its mechanism of antitumor activity in human gastric cancer
cell line SGC7901. Professor Li and his colleagues found that Alisol B acetat could
inhibit the proliferation of SGC7901 cell in a time and dose dependent manner. Among the
various phases of cell cycle, the percentage of cells in S phase was significantly
decreased, while the percentage of cells in G1 phase was increased. Flow cytometry assay
also showed Alisol B acetate had positive effect on apoptosis. Typical apoptotic
morphology such as condensation and fragmentation of nuclei and formation of apoptotic
bodies could be observed through electron microscope and phase-contrast microscope.
Further investigating the molecular mechanism behind Alisol B acetat -induced apoptosis,
cells treated with Alisol B acetat underwent a rapid loss of mitochondrial transmembrane
potential, activition of caspase-3, -9, upregulation of Apaf-1 and Bax, and inhibition of
the PI3K/Akt in a time-dependent manner. The researches domenstrated for the first time
that Alisol B acetate induced human gastric cancer apoptosis through regulation of
mitochondrial and PI3K/AKT signaling pathways Their research results indicate that Alisol
B acetate might be used to treat gastric cancer , one of the most common cancers
worldwide. By knowing the mechanism of action of Alisol B acetate, it may provide a new
therapeutic option, as a potential anticancer agent, in the treatment of gastric cancer.
Study could help target new
pancreatitis treatments
Pancreatitis is often a fatal condition, in which the pancreas digests itself and
surrounding tissue. Scientists have previously found that alcohol can trigger the
condition by combining with fatty acids in the pancreas, which leads to an excessive
release of stored calcium ions. Once calcium ions enter cell fluid in the pancreas it
activates digestive enzymes and damages the cells. The team, in collaboration with the
RIKEN Brain Science Institute in Japan, have now identified channels within special stores
that allow calcium to enter the fluid inside pancreatic cells. They have also found that
toxic calcium release can be significantly reduced if the gene responsible for the
production of these channels is ‘deleted’ (or knocked-out). Professor Ole
Petersen, from the University’s School of Biomedical Sciences, explains: “The
pancreas releases enzymes into the gut, where they become activated and digest our food.
When these digestive enzymes are activated inside the cells, however, they start to digest
the pancreas itself, causing serious damage and often death. Alcohol is widely recognised
as one of the triggers for this process, but the reasons behind it have been unclear.
New, less invasive genetic test
greatly improves pregnancy rates in older women with poor prognosis
A new test examining chromosomes in human eggs a few hours after fertilisation can
identify those that are capable of forming a healthy baby, a researcher told the 25th
annual conference of the European Society of Human Reproduction and Embryology today
(Monday 29 June). Dr. Elpida Fragouli, from the Department of Obstetrics and Gynaecology,
University of Oxford, UK, and Reprogenetics UK, said that her team’s work had already
enabled seven ongoing pregnancies in a group of older women with a history of multiple
failed IVF attempts. “Out of 35 patients who had embryo transfers after the test, we
achieved a pregnancy rate of 20%, which is exceptional considering the extremely poor
prognosis of the women involved.” she said. “This represents a doubling of the
usual pregnancy rate for women who fall into this category, which is otherwise, at best,
under 10% and, at worst, zero. To date, we have two live births from this group, and all
the other women who became pregnant have maintained their pregnancies. The study is
continuing, and we believe that we will achieve more pregnancies with the help of this
technology in the future.” The scientists used the Comparative Genomic Hybridisation
(CGH) technique to count the chromosomes in each egg. Unlike conventional screening
strategies, using the fluorescent in situ hybridisation (FISH) method, which allows less
than half of the chromosomes of an embryonic cell to be examined, CGH enables the
evaluation of the entire chromosome complement. CGH was used to examine the fertilised
eggs by looking at polar bodies, tiny cells that are a by-product of egg development. The
chromosomes of polar bodies provide an indication of whether the corresponding egg is
normal or abnormal; if the polar bodies have the wrong number of chromosomes, so does the
egg.
High levels of cycling training
damage sperm – what can be done to protect triathletes from infertility?
The high-intensity training undertaken by triathletes has a significant impact on the
quality of their sperm, the 25th annual conference of the European Society of Human
Reproduction and Embryology heard today (Monday 29 June). Professor Diana Vaamonde, from
the University of Cordoba Medical School, Cordoba, Spain, said that the triathletes who
did the most cycling training had the worst sperm morphology. Professor Vaamonde’s
team has previously shown that both high exercise intensity and high exercise volume may
be detrimental to sperm quality. They decided to take a more profound look at the
sportsmen who seemed to show the greatest alteration – the triathletes – and
assess the correlation between the volume of training in each activity and sperm quality.
Of the three modalities, only cycling, the activity for which triathletes undertake the
most training, showed a clear correlation with sperm quality. The more cycling training
the sportsmen undertook, both in time and kilometres, the worse their sperm quality
became.
Dutch researchers find first
evidence that female human embryos adjust the balance of X
Dutch researchers have found the first evidence that a process of inactivating the X
chromosome during embryo development and implantation, which was known to occur in mice
but unknown in humans, does, in fact, take place in human female embryos prior to
implantation in the womb. Ms Ilse van den Berg told the 25th annual meeting of the
European Society of Human Reproduction and Embryology in Amsterdam today (Monday) that her
findings may have implications for the laboratory cultures that embryos are grown in
before transfer to a woman’s womb during fertility treatment, as well as for embryo
stem cell research. Males and females have two sex chromosomes: X and Y. While females
have two X chromosomes and no Y chromosome, males have one of each. As the X chromosome is
much larger then the Y chromosome, males and females also differ in their numbers of genes
and gene expression. To equalise this difference in gene expression, females need to
silence one X chromosome in every cell – a process known as X chromosome inactivation
(or XCI).
C-section births cause genetic
changes that may increase odds for developing diseases in later life
Swedish researchers have discovered that babies born by Caesarean section experience
changes to the DNA pool in their white blood cells, which could be connected to altered
stress levels during this method of delivery, according to the July issue of Acta
Paediatrica. It is thought that these genetic changes, which differ from normal vaginal
deliveries, could explain why people delivered by C-section are more susceptible to
immunological diseases such as diabetes and asthma in later life, when those genetic
changes combine with environmental triggers. Blood was sampled from the umbilical cords of
37 newborn infants just after delivery and then three to five days after the birth. It was
analysed to see the degree of DNA-methylation in the white blood cells - a vital part of
the immune system. This showed that the 16 babies born by C-section exhibited higher
DNA-methylation rates immediately after delivery than the 21 born by vaginal delivery.
Three to five days after birth, DNA-methylation levels had dropped in infants delivered by
C-section so that there were no longer significant differences between the two groups.
“Delivery by C-section has been associated with increased allergy, diabetes and
leukaemia risks” says Professor Mikael Norman, who specialises in paediatrics at the
Karolinska Institutet in Stockholm, Sweden. “Although the underlying cause is
unknown, our theory is that altered birth conditions could cause a genetic imprint in the
immune cells that could play a role later in life.
Fish intake of Swedish male
adolescents is a predictor of cognitive performance
Frequent fish intake at age 15 was associated with significantly higher cognitive
performance 3 years later.
Agrichemicals in surface water and
birth defects in the United States
Elevated concentrations of agrichemicals in surface water in April–July coincided
with higher risk of birth defects in live births with LMPs April–July. While a causal
link between agrichemicals and birth defectscannot be proven from this study an
association might provide clues to common factors shared by both variables.
Reported symptoms of food
hypersensitivity and sensitization to common foods in 4-year-old children
FHS was reported in 11% of the children (n = 397). Eczema was the most commonly reported
symptom and the only symptom in half of these children. Food-related reactions from the
airways, facial oedema or urticaria were reported in 198 children, and the majority of
these children (75%) reported multiple symptoms. Furthermore, a combination of airway
symptoms, facial oedema or urticaria together with sensitization to food suggested a more
severe form of FHS. This was found in 1.6% of all children. Symptoms caused by peanut were
closely associated with sensitization to peanut (p < 0.001). Food hypersensitivity in
4-year-old children with any of asthma, rhino-conjunctivitis, facial oedema or urticaria
in combination is in most cases associated to sensitization to food. This phenotype of FHS
is likely to represent a more severe form of food hypersensitivity.
Could Estrogen Improve Outcomes
After Traumatic Brain Injury, Shock?
UT Southwestern Medical Center researchers are conducting two pilot clinical trials to
determine whether a single, early dose of estrogen can improve survival and neurological
outcomes after severe traumatic brain injury or traumatic hemorrhagic shock. In these
double-blind studies, male patients transported to Parkland Memorial Hospital following
severe traumatic brain injury or severe blood loss associated with a traumatic injury will
be assigned randomly to receive either Premarin (estrogen) or a placebo intravenously
after arriving in the emergency department. Estrogen or a placebo will be administered as
a single-dose within two hours of injury. The researchers will measure biomarkers of
injury and repair in different body fluids during the first few days after injury, and
also will evaluate survival and neurological outcomes. Despite advances in surgical
interventions and intensive care management, about 35 percent of patients with severe
traumatic brain injury and hemorrhagic shock die. Many survivors do not fully recover and
are left with permanent disability.“Following traumatic brain injury or hemorrhagic
shock, secondary injury, such as inflammation, begins rapidly and greatly worsens the
initial injury,” said Dr. Jane Wigginton, assistant professor of emergency medicine
at UT Southwestern and the trials’ principal investigator. “Hundreds of animal
studies have shown that estrogen significantly reduces secondary injury. Those studies
give us hope that this new therapy offers considerable promise and minimal risk following
one dose in patients with life-threatening traumatic injuries.”
Site for Alcohol’s Action in
the Brain Discovered
Alcohol's inebriating effects are familiar to everyone. But the molecular details of
alcohol's impact on brain activity remain a mystery. A new study by researchers at the
Salk Institute for Biological Studies brings us closer to understanding how alcohol alters
the way brain cells work.
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