News - Week 18 - 2009
Alterations in vitamin D status and
anti-microbial peptide levels in patients in the intensive care unit with sepsis
This study demonstrates an association
between critical illness and lower 25(OH)D and DBP levels in critically ill patients as
compared to healthy controls. It also establishes a positive association between vitamin D
status and plasma LL-37, which suggests that systemic LL-37 levels may be regulated by
vitamin D status. Optimal vitamin D status may be important for innate immunity especially
in the setting of sepsis. Further invention studies to examine this association are
warranted.
Identified a molecule that
increases the risk of cardiac insufficiency
A team of scientists from the Center for
Applied Medical Research (CIMA) of the University of Navarra has identified a key enzyme
in the development of cardiac insufficiency. This enzyme is involved in the accumulation
of fibrous tissues in the hearts of patients with chronic cardiac diseases and
deterioration of heart functions.
The research project, published in the journal Hypertension, is part of a project of the
Red Europea de Excelencia en Hipertensión y Enfermedades Cardiovasculares
[European Network of Excellence in Hypertension and Cardiovascular Diseases], in which
research groups from Belgium, the Netherlands, Italy, Great Britain, France, Germany,
Finland and Poland are all participating. The project also forms part of the Red
Española de Investigación de las Enfermedades Cardiovasculares [Spanish Network
for Research on Cardiovascular Diseases].
MR Enterography Eliminates
Unnecessary Radiation Exposure in Patients with Small Bowel Disease
MR enterography is an effective tool to
evaluate and guide treatment of patients with Crohns Disease (a common form of
inflammatory bowel disease that typically affects young people) without exposing them to
radiation, according to a study performed at the Warren Alpert School of Medicine/Brown
University in Providence, RI. MR enterography is an MR examination targeted at the
small bowel. The study included approximately 100 patients and 15 physicians, said
David Grand, MD, lead author of the study. Nearly one-hundred percent of physicians
who use MR enterography reported that they found information from the test useful for
guiding patient management; patients overwhelmingly preferred MR to the CT, he said.
This is an ongoing study, he added. Crohns disease typically
effects young people and will be a chronic disease throughout their life, requiring them
to have multiple diagnostic imaging procedures. These young patients are too often exposed
to multiple doses of ionizing radiation, the long-term effects which may be quite
dangerous. Additionally, patients are often given very effective but potentially toxic
biologic therapies to help reduce inflammation, said Dr. Grand. MR
can also be used to see if these agents are working without exposure to radiation,
he said.
Majority of Ordering Physicians
Lack Knowledge of Radiation Exposure Risks from CT
Ordering physicians have limited knowledge
of CT-related radiation exposure and its associated risks, according to a study performed
at the Carilion Clinic in Roanoke, VA.
More than 100 surveys were completed by physicians from various specialties who
order CT scans at a tertiary-care teaching hospital, said Jeremy McBride, MD, lead
author of the study. When physician knowledge regarding radiation was assessed, 63%
underestimated the radiation dose of one abdominal-pelvic CT in chest radiograph
equivalents. When asked if they believed a single abdominal-pelvic CT increases a
patients risk of cancer nearly 80% responded affirmatively; however, 74%
significantly underestimated the risk as published in literature. When asked if they
regularly disclose the risks associated with CT scans with patients, nearly 60% responded
affirmatively; however only 20% said the risk of exposure was part of that
disclosure, said Dr. McBride. When asked if radiation exposure and cumulative
prior radiation exposure influenced their decision, 48% and 59% respectively, responded it
had no or little influence on their decision. Forty-seven percent reported that risk of
litigation significantly influenced their decision to order a CT scan on a given
patient, he said. Ben E. Paxton, MD, and Richard M. Wardrop III, MD, worked with Dr.
McBride on this study. Most of the time, when a CT scan is ordered it can be
justified. When a CT is appropriately ordered patients should be aware that the
examination has been recommended based upon its diagnostic value and that radiation
exposure will be minimized. If patients are concerned, they should feel comfortable asking
their physician how an imaging examination will answer a specific question and how it will
affect their clinical management. They can also make their physician aware of their
concern about radiation exposure from medical imaging and discuss appropriate
alternatives, said Dr. McBride.
Hypertension, Diabetes and
Increased Carotid Artery Wall Thickness Means Increased Risk of Stroke
Increased carotid artery wall thickness
(CAWT), which can cause heart attack and stroke in many patients, is significantly related
to diabetes and hypertension, according to a study performed at A.O.U. in Cagliari
Sardegna, Italy (Chairman, Professor Giorgio Mallarini). During the study, 186 patients
were evaluated using multidetector row CT to see if CAWT is associated with cardiovascular
risk factors such as hypertension, diabetes mellitus, dyslipidemia and a history of
smoking. Results showed that there is a statistically significant relationship between
diabetes and hypertension. There was no significant statistical correlation between
the increase of carotid wall thickness, smoking and dyslipidemia, said Luca Saba,
MD, lead author of the study. Our group demonstrated that the presence of CAWT
greater than 1mm in patients with diabetes or hypertension is strongly correlated with a
risk to suffer a stroke. Patients at higher risk should be monitored every 12
months, said Dr. Saba.
Diffusion Tensor Imaging Allows
Radiologists to See Areas of the Brain Rarely Seen Using Other Imaging Modalities
Radiologists are now able to look at parts
of the brain using diffusion tensor imaging (DTI) that are rarely visible with any other
imaging method, according to a study performed at Beth Israel Deaconess Medical Center in
Boston, MA. DTI data was available in 179 cases. DTI is a technique that measures
diffusion in a series of different spatial directions (XYZ). We used DTI to evaluate the
white matter anatomy (layer found beneath the outer layer of the brain), said Fargol
Booya, MD, lead author of the study. Based on the pattern of color changes, we could
somewhat predict whether white matter tracts were displaced. Evaluation of white matter
anatomy is usually not possible with any other imaging method. Tumor (21 patients),
hemorrhage (15 patients) and infarction (27 patients) had different manifestations on
DTI, she said. This method offers an overall view of brain anatomy, including
the degree of connectivity between the different regions of the brain. Characterization of
sensorimotor pathways or language center involvement by acute ischemic insults has a
strong correspondence to clinical symptoms, prognosis and long-term management, said
Dr. Booya.
New Womens Imaging Technique
Allows for a More Accurate Diagnosis of Breast Cancer
Breast elastography allows physicians to
give a more accurate diagnosis of breast cancer, according to a study performed at
Singapore General Hospital in Singapore. Breast elastography is a new technique which
looks at the mechanical properties of tissues (relative stiffness) as opposed to
conventional ultrasound which looks at the backscatter of transmitted ultrasound waves
through tissues. Ninety-nine women with 110 sonographically visible lesions were evaluated
with ultrasound, elastography and combined ultrasound and elastography. 26 lesions were
malignant and 84 were benign on histology. All breast cancers (100%) in the study
were diagnosed correctly by elastography alone compared to 88.5% by conventional
ultrasound, said Llewellyn Sim, MD, lead author of the study. The use of
breast elastography alone or combined with ultrasound provides a more accurate diagnosis
of breast cancer, said Dr. Sim.
Breast elastography improves the sonographic diagnosis of breast cancer. It also
potentially reduces unnecessary work-up i.e. biopsies of benign breast lesions and patient
anxiety, he said.
OSU abuses dogs, PETA says
A controversial animal rights group is
accusing George Billman, a professor of physiology and cell biology at Ohio State, of
abusing dogs used in his research. According to PETA, Billman has called for experiments
that require a surgical operation on dogs to insert a cuff around an artery. The dog then
runs on a treadmill while the cuff is tightened, inducing a heart attack.
Muscle deterioration in patients
with lung disease seen connected to CO2
Muscle deterioration in patients with lung
diseases might be a direct consequence of high carbon dioxide levels in their blood, an
international team of researchers headed by Prof. Yosef Gruenbaum of the Hebrew University
of Jerusalem has found. The incidence of lung diseases continues to increase in the
world's populations. For example, one in seven persons in the UK is affected by some form
of chronic lung disease, most commonly chronic obstructive pulmonary disease (COPD) and
asthma. Many of these diseases also cause, in the worst cases, muscle deterioration as
well as elevated levels of carbon dioxide (hypercapnia) in the bloodstream. In a normal
situation, the lungs allow for a proper balance of oxygen from the atmosphere reaching the
bloodstream and carbon dioxide from the bloodstream being transferred to the atmosphere.
It is still a matter of some controversy whether the high carbon dioxide levels in
patients with chronic lung disease actually cause damage to those patients and
specifically whether the loss of muscle is a consequence of those heightened levels.
MicroRNA may link smoking risk gene
to neurobiology of addiction
During the past several years, significant
progress has been made in identifying susceptibility genes for nicotine dependence through
genetic linkage and association analyses. Although a large number of genes have been
associated with tobacco smoking, only a very limited number of genetic variants are
considered to be causative. How to find these functional variants and then characterize
them remains challenging in the field of human genetics. In the traditional genetic dogma,
DNA codes for RNA and RNA codes for protein. But what about the leftover bits of RNA that
do not seem to code for proteins? One type of RNA 'leftovers' is the microRNAs. These
small pieces of RNA do not code for proteins. Instead, they influence the extent to which
other genes are expressed, i.e., the rate or extent of conversion of DNA to RNA. To date,
there have been relatively few examples of the direct involvement of microRNAs in
psychiatric disorders.
Liver disease responsible for most
alcohol-related illness and deaths
Liver disease is the most prevalent cause
of alcohol-related deaths, followed by car accidents and cancer, according to new research
conducted in Portugal and presented today at EASL 2009, the Annual Meeting of the European
Association for the Study of Liver in Copenhagen, Denmark. The study also showed that
alcohol-related diseases account for 1.25% of the health expenditure in Portugal. The
study, aimed at assessing the burden of diseases attributable to alcohol consumption,
showed that 3.8% of all deaths in Portugal are related to alcohol consumption and account
for a death toll of 4,054 people every year. Within these, most people are killed by liver
disease (28.3%, representing 1,147 individuals), followed by car accidents (26.2%,
representing 1,062 individuals) and by different types of cancers associated with alcohol
consumption 21%, representing 851 individuals). According to the study, the burden of
alcohol-related diseases in Portugal is 5.0%, which is higher than the global statistic
estimated by the World Health Organization (WHO) of about 3.2%. This is the first study
designed to estimate the burden of disease attributable to alcohol consumption,
specifically in Portugal. Professor Helena Cortez-Pinto, Unidade de de Nutrição e
Metabolismo, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de
Lisboa, who led the study, said: "The results of the study confirm that alcohol is an
important health risk factor that is particularly related to liver disease in Portugal. By
quantifying the significant impact alcohol has on the nation's health, we highlight the
need for effective strategies to promote lifestyle changes and moderate alcohol
consumption to reduce death rates, the incidence of liver disease and related costs to the
healthcare system." In this study, researchers estimated the burden and cost of
diseases attributable to alcohol drinking based on the demographic and health statistics
available for 2005. The results indicate that 14.1 million is attributable to
alcohol-related chronic disease admissions (liver diseases, cancer, etc.) and 82.2
million to acute alcohol-related conditions (traffic accidents and external causes),
resulting in a total amount of 96.3 million. Furthermore, ambulatory costs of
alcohol-related diseases were estimated as 93 million, totaling 189.2 million
direct costs attributable to alcohol, which represent 0.13% of the Portuguese Gross
Domestic Product and 1.25% of total national health expenditures.
Vitamin D levels linked to asthma
severity
New research provides evidence for a link
between vitamin D insufficiency and asthma severity. Serum levels of vitamin D in more
than 600 Costa Rican children were inversely linked to several indicators of allergy and
asthma severity, including hospitalizations for asthma, use of inhaled steroids and total
IgE levels, according to a study that will appear in the first issue for May of the
American Journal of Respiratory and Critical Care Medicine. While previous in vitro
studies have suggested that vitamin D may affect how airway cells respond to treatment
with inhaled steroids, this is the first in vivo study of vitamin D and disease severity
in children with asthma. Juan Celedón, M.D., Dr. P.H. and Augusto Litonjua, M.D., M.P.H.
of Harvard Medical School and colleagues recruited 616 children with asthma living in the
Central Valley of Costa Rica, a country known to have a high prevalence of asthma. Each
child was assessed for allergic markers, including both allergen-specific and general
sensitivity tests, and assessed for lung function and circulating vitamin D levels.
Children whose forced expiratory volume in one second (FEV1) exceeded 65 percent of the
predicted value were also tested for airway reactivity.
They found that children with lower vitamin D levels were significantly more likely to
have been hospitalized for asthma in the previous year, tended to have airways with
increased hyperreactivity and were likely to have used more inhaled corticosteroids, all
signifying higher asthma severity. These children were also significantly more likely to
have several markers of allergy, including dust-mite sensitivity.
"To our knowledge this is the first study to demonstrate an inverse association
between circulating levels of vitamin D and markers of asthma severity and allergy,"
wrote Drs. Celedón and Litonjua "While it is difficult to establish causation in a
cross-sectional study such as this, the results were robust even after controlling for
markers of baseline asthma severity." "This study suggests that there may be
added health benefits to vitamin D supplementation" said Dr. Celedón. Current
recommendations for optimal vitamin D levels geared toward preserving bone health, such as
preventing rickets in children and osteoporosis in adults.
Benefit of grapes may be more than
skin deep
Can a grape-enriched diet prevent the
downhill sequence of heart failure after years of high blood pressure? A University of
Michigan Cardiovascular Center study suggests grapes may prevent heart health risks beyond
the simple blood pressure-lowering impact that can come from a diet rich in fruits and
vegetables. The benefits may be the result of the phytochemicals naturally
occurring antioxidants turning on a protective process in the genes that reduces
damage to the heart muscle. The study, performed in laboratory rats, was presented at the
2009 Experimental Biology convention in New Orleans. The researchers studied the effect of
regular table grapes (a blend of green, red, and black grapes) that were mixed into the
rat diet in a powdered form, as part of either a high- or low-salt diet. Comparisons were
made between rats consuming the grape powder and rats that received a mild dose of a
common blood pressure drug. All the rats were from a research breed that develops high
blood pressure when fed a salty diet. After 18 weeks, the rats that received the
grape-enriched diet powder had lower blood pressure, better heart function, and fewer
signs of heart muscle damage than the rats that ate the same salty diet but didn't receive
grapes. Rats that received the blood pressure medicine, hydrazine, along with a salty diet
also had lower blood pressure, but their hearts were not protected from damage as they
were in the grape-fed group. "There are the small changes that diet can bring, but
the effect of grape intake on genes can have a greater impact on disease down the
road," said E. Mitchell Seymour, M.S., who led the research as part of his doctoral
work in nutrition science at Michigan State University. He manages the U-M
Cardioprotection Research Laboratory, which is headed by U-M cardiac surgeon Steven
Bolling, M.D. Heart cells, like other cells in the body, make an antioxidant protein
called glutathione, which is one of our first defenders against damaging oxidative stress.
High blood pressure causes oxidative stress in the heart and lowers the amount of
protective glutathione. However, intake of grapes actually turned on
glutathione-regulating genes in the heart and significantly elevated glutathione levels.
This may explain why the hearts of grape-fed animals functioned better and had less
damage.
New imaging analysis predicts brain
tumor survival
As early as one week after beginning
treatment for brain tumors, a new imaging analysis method was able to predict which
patients would live longer, researchers from the University of Michigan Comprehensive
Cancer Center have found. The method uses a standard magnetic resonance imaging, or MRI,
protocol to monitor changes over time in tumor blood volume within individual voxels of
the image, rather than a composite view of average change within the tumor. This
parametric response map allowed researchers to see specific areas in which tumor blood
volume increased or decreased, that may have canceled each other out when looking at the
changes as an average. Results of the study appear in the advance online edition of Nature
Medicine. What we have potentially is a generalized analytical approach that we can
use to quantify treatment intervention in patients, says study author Brian Ross,
Ph.D., professor of radiology and biological chemistry at the U-M Medical School and
co-director of the Molecular Imaging Program at the U-M Comprehensive Cancer Center.
The Price of Pain and the Value of
Suffering
During these trying financial times, the
cost of healthcare and how much we are willing to pay for it is at the top of our economic
concerns. The financial value of pain has a wide ranging influence, affecting drug prices
and injury compensation. But what about on an individual level is it possible to
place a value on our health, to prevent pain and suffering? University College London
psychologists Ivo Vlaev and Nick Chater, and neuroscientists Ben Seymour and Raymond J.
Dolan were interested in just how much money volunteers were willing to pay to avoid pain
and discomfort. Study participants were given money, with the understanding that they
could keep for themselves whatever cash remained. They experienced one pulse of electric
shock and then had to indicate how much money they would pay in order to avoid receiving
15 more shocks of the same intensity. Then, a computer program would determine how much
the volunteers would actually have to pay. The program would randomly select a dollar
amount if that amount was higher than what the participants were willing to pay,
then the participants would be shocked. However, if the computer's price was lower than
the participant's price, then they would pay the computer's price and avoid the pain. The
volunteers were informed that the computer selection would be completely random, so it was
really in their best interest to select a price that accurately reflected how they value
the pain from the electric shock. For each volunteer, this process was repeated a number
of times, with differing intensities of shocks. The results, described in Psychological
Science, a journal of the Association for Psychological Science, reveal that demand for
pain relief is almost completely dependent on pain experienced in the recent past and the
available cash on hand. That is, the participants were willing to pay more money to avoid
pain if that pain was more intense compared to previous trials. In addition, the price
they were willing to pay was based on what they were given (money-in-the-pocket) rather
than on their overall wealth.These findings suggest that the value we place on relief from
suffering is flexible and that activity of health markets cannot be predicted by the
behavior of individuals.
LSUHSC public health researcher
finds reason for weight gain
iwei Chen, MD, PhD, Assistant Professor of
Epidemiology at the LSU Health Sciences Center New Orleans School of Public Health, is the
lead author of a research paper showing that weight gain and obesity are more linked to an
increase in liquid calories, particularly sugar-sweetened beverages, than calories from
solid food. To our knowledge, this is the first study to document the relative effects of
calories from liquids compared with those of calories from solid food on weight loss in
adults over an extended period. The study is published in the May 1, 2009 issue of the
American Journal of Clinical Nutrition. The study reports four principal findings: First,
a reduction in liquid calorie intake was significantly associated with weight loss at both
6 months and 18 months. Second, the weight-loss effect of a reduction in liquid calorie
intake was stronger than that of a reduction in solid calorie intake. Third, a reduction
in sugar-sweetened beverage intake was significantly associated with weight loss at both 6
and 18 months. Fourth, no other beverage type was associated with weight change. It has
been projected that 75% of US adults will be overweight or obese by 2015. "Today,
Americans consume 150-300 more calories a day than they did 30 years ago," notes Dr.
Chen, "and caloric beverages account for approximately 50% of this increase."
The researchers followed 810 men and women, 25-79 years old, whose 24 hour dietary intake
recall was measured by telephone interviews conducted when they entered the study and at 6
and 18 months. Beverages were divided into 7 categories based upon calorie content and
nutritional composition.
German researchers make significant
strides in identifying cause of bacterial infections
Several bacterial pathogens use toxins to
manipulate human host cells, ultimately disturbing cellular signal transduction. Until
now, however, scientists have been able to track down only a few of the proteins that
interact with bacterial toxins in infected human cells. Now, researchers of the Max Planck
Institute of Biochemistry in Martinsried and the Max Delbrück Center for Molecular
Medicine (MDC) Berlin-Buch in Germany have identified 39 interaction partners of these
toxins, using novel technology which allowed them to screen for large numbers of proteins
simultaneously (Cell Host & Microbe, Vol. 5, Issue 4, 397-403)*. Many bacteria inject
toxins into human cells using a secretion system that resembles a molecular syringe.
Within the host cell, some of these toxins are activated in such a way that they can
manipulate important cellular signaling pathways. In healthy cells, these signals serve to
regulate metabolism or cell division, among other things. By manipulating the signals,
bacteria can abuse the cell machinery of the human host in order to spread and survive.
Applying a method developed by Professor Matthias Mann of the MPI, the scientists
succeeded for the first time in systematically investigating the cellular target sites of
the bacterial toxins. "Surprisingly, the toxins are not optimally adapted to the
structures of human proteins," Dr. Matthias Selbach of MDC explained. While binding
relatively weakly to individual human proteins, they are able to influence several
different proteins simultaneously. "A single bacterial toxin seems to function like a
master key that can access different host cell proteins in parallel", Dr. Selbach
said. "Perhaps it is due to this strategy that bacteria are able to attack very
different cells and, thus, to increase their survival chances in the host." Dr.
Selbach hopes that these basic research findings will help to improve the treatment of
bacterial infections in the future. Instead of nonspecific antibiotic therapy, new drugs
could target the signaling mechanisms which are disrupted by the bacterial toxins.
Eating fatty fish once a week
reduces men's risk of heart failure
Eating salmon or other fatty fish just once
a week helped reduce men's risk of heart failure, adding to growing evidence that omega-3
fatty acids are of benefit to cardiac health. Led by researchers at Beth Israel Deaconess
Medical Center (BIDMC) and reported in today's on-line issue of the European Heart
Journal, the findings represent one of the largest studies to investigate the association.
"Previous research has demonstrated that fatty fish and omega-3 fatty acids help to
combat risk factors for a range of heart-related conditions, such as lowering
triglycerides [fats in the blood] reducing blood pressure, heart rate and heart rate
variability," explains first author Emily Levitan, PhD, a research fellow in the
Cardiovascular Epidemiology Research Center at BIDMC. "Collectively, this may explain
the association with the reduced risk of heart failure found in our study." A
life-threatening condition that develops when the heart can no longer pump enough blood to
meet the body's needs, heart failure (also known as congestive heart failure) is usually
caused by existing cardiac conditions, including high blood pressure and coronary artery
disease. Heart failure is the leading cause of hospitalization among patients 65 and
older, and is characterized by such symptoms as fatigue and weakness, difficulty walking,
rapid or irregular heartbeat, and persistent cough or wheezing. The researchers followed
39,367 Swedish men between the ages of 45 and 79 from 1998 to 2004. The researchers
recorded details of the men's diet and tracked the men's outcome through Swedish inpatient
hospital registers and cause-of-death registers. During this period, 597 men in the study
(with no previous history of heart disease or diabetes) developed heart failure.
Thirty-four men died. Analysis of their numbers showed that the men who ate fatty fish
(herring, mackerel, salmon, whitefish and char) once a week were 12 percent less likely to
develop heart failure, compared with men who ate no fatty fish. Although this association
did not reach statistical significance, notes Levitan, the researchers also found a
statistically significant association with the intake of marine omega-3 fatty acids, which
are found in cod liver and other fish oils: The men who consumed approximately 0.36 grams
a day were 33 percent less likely to develop heart failure than the men who consumed
little or no marine omega-3 fatty acids. "We divided the men into five groups based
on their intake of fatty fish," explains Levitan. "The first group consumed
little or no fatty fish; at the other end of the spectrum, the fifth group consumed
significant quantitities, three or more servings per week. We found that while the 'middle
group' who ate one serving per week had a 12 percent reduced risk of heart
failure, the next two groups, who ate either two servings a week or three or more servings
a week, had nearly the same heart failure risk as the men who ate no fish at all."
Pesticide exposure found to
increase risk of Parkinson's disease
The fertile soil of California's Central
Valley has long made it famous as one of the nation's prime crop-growing regions. But it's
not just the soil that allows for such productivity. Crops like potatoes, dry beans and
tomatoes have long been protected from bugs and weeds by the fungicide maneb and the
herbicide paraquat. Scientists know that in animal models and cell cultures, such
pesticides trigger a neurodegenerative process that leads to Parkinson's disease. Now,
researchers at UCLA provide the first evidence for a similar process in humans. In a new
epidemiological study of Central Valley residents who have been diagnosed with Parkinson's
disease, researchers found that years of exposure to the combination of these two
pesticides increased the risk of Parkinson's by 75 percent. Further, for people 60 years
old or younger diagnosed with Parkinson's, earlier exposure had increased their risk for
the disease by as much as four- to six-fold. Reporting in the April 15 issue of the
American Journal of Epidemiology, Beate Ritz, professor of epidemiology at the UCLA School
of Public Health, and Sadie Costello, a former doctoral student at UCLA who is now at the
University of California, Berkeley, found that Central Valley residents who lived within
500 meters of fields sprayed between 1974 and 1999 had a 75-percent increased risk for
Parkinson's.In addition, people who were diagnosed with Parkinson's at age 60 or younger
were found to have been at much higher risk because they had been exposed to maneb,
paraquat or both in combination between 1974 and 1989, years when they would have been
children, teens or young adults. The researchers enrolled 368 longtime residents diagnosed
with Parkinson's and 341 others as a control group.
Controlling our brains
perception of emotional events
Research performed by Nicole Lauzon and Dr.
Steven Laviolette of the Schulich School of Medicine & Dentistry at The University of
Western Ontario has found key processes in the brain that control the emotional
significance of our experiences and how we form memories of them. A lack of proper brain
function in this area is what lies beneath such conditions as Schizophrenia and
Post-Traumatic Stress Disorder (PTSD). In people who suffer from these conditions
emotional experiences can become distorted, causing the person to lose touch
with reality. The findings have been published online by The Journal of Neuroscience.
Lauzon, a Doctoral graduate student in the Laviolette laboratory, discovered that specific
receptors for the neurotransmitter dopamine can control how the brain processes
emotionally significant information as well as memories for those experiences. Using a
rodent model of emotional learning and memory formation, the researchers found by
increasing the activity of a specific dopamine receptor in a region of the brain called
the pre-frontal cortex, it was able to transform a normally insignificant emotional
experience into a very strong emotional memory. In contrast, when a different subtype of
the dopamine system was activated, it was able to block the ability to recall an
emotionally charged experience. Our findings have profound implications for
understanding how specific brain receptors can control the magnitude of emotional
experience and memory formation, says Laviolette.
Acupuncture Eases Radiation-Induced
Dry Mouth in Cancer Patients
Twice weekly acupuncture treatments relieve
debilitating symptoms of xerostomia - severe dry mouth - among patients treated with
radiation for head and neck cancer, researchers from The University of Texas M. D.
Anderson Cancer Center report in the current online issue of Head & Neck. Xerostomia
develops after the salivary glands have been exposed to repeated doses of therapeutic
radiation. People who have cancers of the head and neck typically receive large cumulative
doses, rendering the salivary glands incapable of producing adequate saliva, said Mark S.
Chambers, M.S., D.M.D., a professor in the Department of Dental Oncology. Saliva
substitutes, lozenges and chewing gum bring only temporary relief, and the commonly
prescribed medication, pilocarpine, has short-lived benefits and bothersome side effects
of its own. "The quality of life in patients with radiation-induced xerostomia is
profoundly impaired," said Chambers, the study's senior author. "Symptoms can
include altered taste acuity, dental decay, infections of the tissues of the mouth, and
difficulty with speaking, eating and swallowing. Conventional treatments have been less
than optimal, providing short-term response at best." M. Kay Garcia, LAc, Dr.P.H., a
clinical nurse specialist and acupuncturist in M. D. Anderson's Integrative Medicine
Program and the study's first author, noted that patients with xerostomia may also develop
nutritional deficits that can become irreversible.
Study Finds Blood Cells Can Be
Reprogrammed to Act as Embryonic Stem Cells
In a recent study, U.S. researchers have
reprogrammed cells found in circulating blood into cells that are molecularly and
functionally indistinguishable from embryonic stem cells, a revolutionary achievement that
provides a readily accessible source of stem cells and an alternative to harvesting
embryonic stem cells. The findings were prepublished online in Blood, the official journal
of the American Society of Hematology.
Embryonic stem cells have long been coveted for their potential to treat a multitude of
diseases as a result of their unique properties of nearly indefinite self-renewal and
pluripotency (the ability to develop into any type of cell in the body), but their use has
been the subject of political controversy. Our findings provide the first proof that
cells from human blood can morph into stem cells, said senior study author George Q.
Daley, MD, PhD, an investigator for the Howard Hughes Medical Institute at Childrens
Hospital, Boston. Making pluripotent stem cells from blood, which is one of the
easiest tissues to obtain, provides an easy strategy for generating patient-specific stem
cells that are valuable research tools and may one day be used to treat a number of
diseases. To generate induced pluripotent stem cells (dubbed iPS cells), blood was
collected from a 26-year-old male donor. From the blood sample, the researchers isolated
CD34+ cells, a type of stem cell that produces only blood cells, and cultured them in
growth factors for six days to increase their number. During the culture, the scientists
infected the CD34+ cells with viruses carrying reprogramming factors, genes normally
expressed in embryonic stem cells that can reset the blood cells to an embryonic state.
Colonies of cells exhibiting physical characteristics similar to embryonic stem (ES) cells
appeared about two weeks after the procedure. To determine whether these cells were also
functionally similar to ES cells, the scientists analyzed the CD34+ iPS cell lines to see
if they had acquired stem cell markers, the unique combination of proteins
that coat the cells surface and distinguish them from other types of cells. Indeed,
the iPS cell lines expressed the same markers as ES cells and further shared the capacity
to differentiate into a variety of specialized cell types.
Researchers probe kidney damage,
protection in lupus
Kidney damage associated with the
autoimmune disease lupus is linked to a malfunction of immune cells that causes them to
congregate in and attack the organs, researchers at UT Southwestern Medical Center have
discovered in a mouse study. In a separate study with an international team, the
researchers also found that a certain set of genes appears to protect the kidneys from a
different sort of immune attack in both mice and humans. These studies, taken
together, uncover two important molecules that underlie the pathology of lupus,
particularly kidney disease, said Dr. Edward Wakeland, chairman of immunology at UT
Southwestern and co-senior author of the studies. In addition, they highlight a
certain molecule as a potential target for treating this disease, he said.
Witnessing violence affects
kids health
Study finds link between exposure to
community violence and a disruption to the stress pathways in the body. School-aged
children who witness violence in urban communities show symptoms of post-traumatic stress.
They also suffer physiological effects with a disruption to their normal cortisol
production pattern during the day, which may have long-term negative effects on their
health. According to Dr. Shakira Franco Suglia, from the Harvard School of Public Health,
and her team lead by Dr. Rosalind J. Wright from Brigham and Womens Hospital,
Harvard Medical School in Boston, USA, because these children are not diagnosed with
post-traumatic stress disorder, these abnormal physiological symptoms are unlikely to be
picked up by their doctors. The study1 has just been published online in Springers
International Journal of Behavioral Medicine.
Sugar On Bacteria Surface Serves As
Base For A Web Of Resistance
The bacteria responsible for chronic
infections in cystic fibrosis patients use one of the sugars on the germs surface to
start building a structure that helps the microbes resist efforts to kill them, new
research shows. Scientists have determined that the bacterial cell-surface sugar, a
polysaccharide called Psl, is anchored on the surface of the bacterium as a helix,
providing a structure that encourages cell-to-cell interaction. When multiple bacterial
cells join together with the help of such a structure, they form what is called a biofilm,
a persistent community of bugs that is able to resist the effects of a human immune
response, as well as antibiotic drugs. In the case of the bacterium being studied,
Pseudomonas aeruginosa, the results of biofilm development can be lethal. Chronic
infection with these bacteria is what causes the death of most patients with cystic
fibrosis, a genetic disease characterized in part by excess mucus in the lungs a
condition that can foster creation of the biofilm.
Too much or too little sleep
increases risk of diabetes
Researchers at Université Laval's Faculty
of Medicine have found that people who sleep too much or not enough are at greater risk of
developing type 2 diabetes or impaired glucose tolerance. The risk is 2½ times higher for
people who sleep less than 7 hours or more than 8 hours a night. The findings were
published recently on the website of the journal Sleep Medicine. The researchers arrived
at this conclusion after analyzing the life habits of 276 subjects over a 6-year period.
They determined that over this timespan, approximately 20% of those with long and short
sleep duration developed type 2 diabetes or impaired glucose tolerance versus only 7%
among subjects who were average duration sleepers. Even after taking into account the
effect attributable to differences in body mass among the subjects, the risk of diabetes
and insulin resistance was still twice as high among those with longer and shorter sleep
duration than average sleepers. The researchers also point out that diabetes is not the
only risk associated with sleep duration. A growing number of studies have shed light on a
similar relationship between sleep and obesity, cardiovascular disease, and overall
mortality. The authors observe that among adults, between 7 and 8 hours of nighttime sleep
appears to be the optimum duration to protect against common diseases and premature death.
Moms who breastfeed less likely to
develop heart attacks or strokes
The longer women breastfeed, the lower
their risk of heart attacks, strokes and cardiovascular disease, report University of
Pittsburgh researchers in a study published in the May issue of Obstetrics &
Gynecology. "Heart disease is the leading cause of death for women, so it's vitally
important for us to know what we can do to protect ourselves," said Eleanor Bimla
Schwarz, M.D., M.S., assistant professor of medicine, epidemiology, and obstetrics,
gynecology and reproductive sciences at the University of Pittsburgh. "We have known
for years that breastfeeding is important for babies' health; we now know that it is
important for mothers' health as well." According to the study, postmenopausal women
who breastfed for at least one month had lower rates of diabetes, high blood pressure and
high cholesterol, all known to cause heart disease. Women who had breastfed their babies
for more than a year were 10 percent less likely to have had a heart attack, stroke, or
developed heart disease than women who had never breastfed. Dr. Schwarz and colleagues
found that the benefits from breastfeeding were long-term ? an average of 35 years had
passed since women enrolled in the study had last breastfed an infant. "The longer a
mother nurses her baby, the better for both of them," Dr. Schwarz pointed out.
"Our study provides another good reason for workplace policies to encourage women to
breastfeed their infants." The findings are based on 139,681 postmenopausal women
enrolled in the Women's Health Initiative study of chronic disease, initiated in 1994.
Dark hair? Don't burn? Your genes
may still put you at risk for melanoma
New genetic research suggests that the
traditional risk factors for melanoma may not be as helpful in predicting risk in all
people as previously thought, according to data presented at the American Association for
Cancer Research 100th Annual Meeting 2009. "Traditionally, a clinician might look at
a person with dark hair who did not sunburn easily and classify them as lower risk for
melanoma, but that may not be true for all people in the population," said Peter
Kanetsky, Ph.D., M.P.H., assistant professor of epidemiology at the University of
Pennsylvania. Kanetsky and his colleagues have identified that genetic variants in MC1R
could help to predict melanoma risk in people who are not usually classified as high risk.
While this link previously has been observed, Kanetsky said it is now time to begin
discussing genetic factors as part of the overall melanoma risk model. For the current
study, researchers analyzed 779 patients with melanoma from the Pigmented Lesion Clinic of
the University of Pennsylvania and compared them with 325 healthy control patients.
Overall, the presence of certain MC1R variants was associated with a more than two-fold
risk of melanoma, but this risk was largely confined to those patients who would not
usually be considered to be at elevated risk.
Researchers identify gene
associated with muscular dystrophy-related vision problems
Skeletal muscle disease and vision deficits
might seem unrelated, but a frog model of muscular dystrophy shows it is not such a leap.
Facioscapulohumeral muscular dystrophy, or FSHD, is the world's third most common type of
muscular dystrophy. It is characterized by progressive skeletal muscle weakening in the
face, shoulders, and upper arms. Over half of FSHD patients (also known as
Landouzy-Dejerine syndrome) also have abnormal blood vessels in the back of the eye, which
can cause vision problems. Over 95% of FSHD patients carry a genetic abnormality proposed
to affect expression of the FRG1 gene, and previous studies of FRG1 in frogs demonstrate
that it is important for skeletal muscle development. Therefore, University of Illinois
scientists investigated the possibility that the FRG1 gene might also be responsible for
the blood vessel abnormalities in FSHD patients' eyes. Their report published in Disease
Models & Mechanisms (DMM), describes how they examined the FRG1 gene in the frog and
found the protein that it encodes for is highly expressed in blood vessels. Additional
experiments show that normal FRG1 protein expression is important for blood vessel growth
and organization.
Natural protein may halt colorectal
cancer's spread
Medical College of Wisconsin Cancer Center
researchers in Milwaukee have learned that a protein, CXCL12, that normally controls
intestinal cell movement, has the potential to halt colorectal cancer spreading. These
studies represent a potential mechanism by which CXL12 may slow cancer spreading.
Controlling this process could lead to new biological therapies for colorectal cancers.
"Colorectal cancer ranks third in cancer-related deaths in the United States in
2008," says principal investigator Michael Dwinell, Ph.D., professor of microbiology
and molecular genetics. "Finding therapies to prevent its spread to secondary organs
would increase patient prognosis considerably." Luke Drury, a graduate student in the
interdisciplinary program for biomedical research at the Medical College, was his research
associate. Their abstract will be presented at the American Association for Cancer
Research meeting in Denver, April 21. Normal intestinal cells stick to underlying
proteins, which provide survival signals to maintain cell health. If they become unstuck,
the floating cells undergo a programmed cell death. In cancer, cells have acquired genetic
changes that allow them to survive during loss of attachment. Previously, the researchers
found that colorectal cancer cells lacked CXCL12 expression. In these studies, they
re-introduced CXCL12 expression in colorectal cancer cells which prevented their ability
to adhere to underlying proteins. Plus, the floating cells underwent programmed cell
death.
Exercise protects against damage
causing leakage in the blood-brain barrier
Regular exercise can prevent the disruption
of the blood brain barrier that normally occurs with a dose of methamphetamine comparable
to that used by heavy meth users. A University of Kentucky study is the first to look at
the protective effects of exercise on the vascular effects of methamphetamine, effects
that have been found clinically to contribute to serious, lasting, and sometimes fatal
cardiovascular and neurological problems. Results of the study, conducted in young male
mice, were reported April 22 at the Experimental Biology 2009 meeting in New Orleans. The
presentation was part of the scientific program of The American Physiological Society.
Principal investigator Dr. Michal Toborek says the level of the protective effects of
exercise on the integrity of the blood brain barrier after the human equivalent of one
gram of methamphetamine was surprising even to the research team. The results provide new
understanding of the mechanisms through which the brain reacts to methamphetamine,
particularly those related to oxidative stress. Results also suggest why exercise might
help delay the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's in
which leakiness of the blood brain barrier is a characteristic. The researchers placed 25
young male mice aged three months, equivalent to the 20s in humans -- in cages
where they had access to exercise wheels. For five weeks, the animals took advantage of
the wheels to run continually. Another 25 young mice were housed in similar cages but
without access to wheels. At the end of this "endurance exercise training"
period, all mice were injected with 10 mg. of methamphetamine over a 24-hour period. All
the mice displayed some of the same effects of meth as seen in humans: they appeared
agitated and increased their physical activity, and their body temperature rose. But in
terms of what was happening in the capillaries of the brain, there was a marked difference
between the mice who had been exercising extensively for the previous five weeks and those
who had been sedentary. In the sedentary group of mice, the small capillaries in the brain
experienced increased oxidative stress, causing the blood brain barrier to become more
permeable. Toxins and inflammatory cells previously prevented from crossing the blood
brain barrier then had access to the brain. The exercise group showed no such changes.
Changes in the blood brain barrier, especially the role of oxidative reactions, have been
little studied in the past, says Dr. Toborek; the University of Kentucky study is the
first to observe that meth administration produced an upregulation of NADPH oxidase, a
major enzyme that causes oxidative stress. This is a significant finding, says Dr.
Toborek, because it delineates a mechanism for how meth causes oxidative stress. It also
was significant that the exercise mice were markedly protected from such upregulation and
consequently from the oxidative stress that weakened the capillaries in the brains of the
non-exercise mice.
New hope for treatment of
neurodegenerative disorder
Researchers from the University of Southern
California have taken an important first step toward protecting against Huntington disease
using gene therapy. Huntington Disease is an incurable neurological disorder characterized
by uncontrolled movements, emotional instability and loss of intellectual faculties. It
affects about 30,000 people in the United States, and children of parents with the disease
have a 50 percent chance of inheriting it themselves. "Our findings allow for the
possibility that controlled over-expression of RCAN1-1L might in the future be a viable
avenue for therapeutic intervention in Huntington disease patients," said Kelvin J.
A. Davies, professor of gerontology in the USC Davis School of Gerontology and professor
of biological sciences in the USC College of Letters, Arts and Sciences. In a paper in the
June 2009 issue of Journal of Biological Chemistry, now available online, Davies and his
coauthors use cell culture findings to show that a form of the gene RCAN1, known as
RCAN1-1L, is dramatically decreased in human brains affected by Huntington disease.
RCAN1-1L was first discovered in Davies' lab. The investigators also show that increasing
levels of RCAN1-1L rescues cells from the toxic effects of Huntington disease, a result
that could someday lead to new avenues of treatment, according to Davies. "Our
discovery offers real hope and may even have wide-ranging implications for a variety of
other important CAG repeat-related diseases," Davies said.
Harvard Medical Students Rebel
Against Pharma-Ties
200 Harvard Medical School STUDENTS are
confronting the administration demanding an end to pharmaceutical industry influence in
the classroom. A front page report in the Business section of the New York Times should
bestir some of Harvard Medical School alumni. 200 Harvard Medical School STUDENTS are
confronting the administration demanding an end to pharmaceutical industry influence in
the classroom. "The students say they worry that pharmaceutical industry scandals in
recent years - including some criminal convictions, billions of dollars in fines, proof of
bias in research and publishing and false marketing claims - have cast a bad light on the
medical profession. And they criticize Harvard as being less vigilant than other leading
medical schools in monitoring potential financial conflicts by faculty members."
Autism is Not Mental Illness: Get
it Out of the DSM
In this month of Autism Awareness, I am
ever so aware of the great disparity for our children on the autism spectrum regarding
their diagnosis and healthcare. It brings to light some major changes that need to take
place in order to not only stop the perpetual, exponentially expanding numbers of children
developing autism, but to provide the already affected children with proper medical care
and treatment.
Agent Orange exposure increases
veterans' risk of aggressive recurrence of prostate cancer
Veterans exposed to Agent Orange are at
increased risk of aggressive recurrence of prostate cancer, researchers report. A study of
1,495 veterans who underwent radical prostatectomy to remove their cancerous prostates
showed that the 206 exposed to Agent Orange had nearly a 50 percent increased risk of
their cancer recurring despite the fact that their cancer seemed relatively nonaggressive
at the time of surgery. And, their cancer came back with a vengeance: the time it took the
prostate specific antigen, or PSA, level to double an indicator of aggressiveness
was eight months versus more than 18 months in non-exposed veterans. "There is
something about the biology of these cancers that are associated with prior Agent Orange
exposure that is causing them to be more aggressive. We need to get the word out,"
says Dr. Martha Terris, chief of urology at the Charlie Norwood VA Medical Center in
Augusta and professor of urology at the Medical College of Georgia School of Medicine.
Mayo Clinic Researchers Formulate
Treatment Combination Lethal To Pancreatic Cancer Cells
A combination of two targeted therapies
packs a powerful punch to kill pancreatic cancer cells in the laboratory, Mayo Clinic
cancer researchers report. With further testing of these drugs that are from classes of
pharmaceuticals already used in patients, the Mayo research may lead to new treatment
opportunities for patients with pancreatic cancer, which is extremely difficult to treat.
Critical turning point can trigger
abrupt climate change
Ice ages are the greatest natural climate
changes in recent geological times. Their rise and fall are caused by slight changes in
the Earth's orbit around the Sun due to the influence of the other planets. But we do not
know the exact relationship between the changes in the Earth's orbit and the changes in
climate. New research from the Niels Bohr Institute indicates that there can be changes in
the CO2 levels in the atmosphere that suddenly reach a critical turning point and with
that trigger the dramatic climate changes. The results are published in the American
journal Paleoceanography.The Earth's climate is essentially contolled by three different
cycles (Milankovitch). All three cycles are caused by the pull of the other planets in the
solar system on the Earth, and one could say that they control the Earth's climate by
causing changes in the Sun's radiation.
1 - The Earth's orbit around the sun is not
completely circular, but slightly elliptical. The orbit is 'elastic' and contracts and
expands in a cycle of 100.000 years. And the closer we are to the Sun, the more solar
radiation and the more heat we receive.
2 - The Earth's axis has a tilt in relation
to the Sun and that is why we have summer and winter. But the tilt is not constant, it
swings between 22 degrees and 24 degrees, and the greater the tilt, the greater the
difference between summer and winter. This cycle takes 40.000 years.
3 - The Earth rotates around on its axis
like a top - this gives day and night. But due to the tilt of the Earth and the elliptical
orbit the direction changes with a cycle of 20.000 years. This results in varation in to
whether the Earth is nearest the Sun during the summer or during the winter.
Solar radiation varies in the two
hemispheres during the summer due to these cycles in the Earth's tilt and the elliptical
orbit and this has profound implications for whether ice caps can build up in the northern
hemisphere, where the largest land areas are.
Human stem cells promote healing of
diabetic ulcers
Treatment of chronic wounds is a continuing
clinical problem and socio-economic burden with diabetic foot ulcers alone costing the NHS
£300 million a year. Scientists in Bristol have found that human foetal stem cells can
effectively be used to treat back leg ischaemic ulcers in a model of type 1 diabetes. The
researchers also found the culture in which the stem cells had been grown mimicked the
wound-healing ability of the cells, suggesting that they could be used as a
"factory" of wound-healing substances. Alternatively, the active ingredients in
the culture, once identified, could be used instead; this would avoid the ethical concerns
of using human foetal stem cells. In humans, diabetic patients with ischaemic foot ulcers
have the worst outcome of all chronic skin wounds, with higher amputation and mortality
rates than patients carrying non-ischaemic ulcers. Topical gels containing single growth
factors have recently been used with some success in non-ischaemic ulcers, but have been
unsuccessful in ischaemic ulcers, which are also resistant to other conventional
treatment. Ischaemia results when the blood supply to a tissue is greatly reduced or
stopped - this can occur in diabetes since it can also cause impaired blood flow in
patients. The healing activity of stem cells is recognised for their ability to separate
into the various component cells of injured tissues, as well as to discharge growth
factors that may encourage the formation of new blood vessels in the patient. Paolo
Madeddu, Professor of Experimental Cardiovascluar Medicine and colleagues at the Bristol
Heart Institute, previously used stem cells in models of back leg ischaemia, showing that
foetal stem cells could be more therapeutically effective than adult stem cells. Foetal
stem cells possess a better ability to multiply and to graft onto host tissue, and to
separate into other cell types to replace those in the damaged tissue. The group led by
Bristol University's Professor Madeddu have found that foetal stem cells accelerate the
closure of ischaemic diabetic ulcers, while stem cells from blood of adult donors are
ineffective. Professor Madeddu, commenting on the research, said: "This is the first
study to demonstrate the healing capacity of local therapy with CD133+ stem cells in a
model of diabetic ischaemic foot ulcer. The foetus-derived cells would be difficult to
obtain for therapeutic applications. However, the finding that conditioned culture is also
effective in stimulating wound healing may have important implications for the cure of the
ischaemic complications of diabetes.
New study finds continued
abstinence is key to increased survival from alcohol-related liver disease
However, the downside is that up a quarter
of people with alcohol-related cirrhosis die before they get the chance to stop drinking.
Alcohol-related cirrhosis develops silently but usually presents with an episode of
internal bleeding or jaundice - which is often fatal. The study, led by Dr Nick Sheron,
senior lecturer at the University of Southampton and consultant hepatologist at
Southampton General Hospital, found that abstinence from alcohol is the key factor in
long-term prognosis, even with relatively severe alcohol-related cirrhosis of the liver.
The study appears in this month's Addiction journal. The aim was to determine the effect
of pathological severity of cirrhosis on survival in patients with alcohol-related
cirrhosis. Liver biopsies from 100 patients were scored for the Laennec score of severity
of cirrhosis between 1 January 1995 and 31 December 2000, and medical notes were reviewed
to determine various clinical factors including drinking status. Using up-to-date
mortality data from the National Health Service Strategic Tracing Service, Dr Sheron found
that drinking status was the most important factor determining long-term survival in
alcohol-related cirrhosis of the liver. He found that the degree of cirrhosis on biopsy
had less impact on survival. Abstinence from alcohol at one month after diagnosis of
cirrhosis was the more important factor determining survival with a seven year survival of
72 per cent for the abstinent patients against 44 per cent for the patients continuing to
drink.
Study identifies genes that protect
against aging
Scientists at the University of Liverpool
have developed a new method to help researchers identify genes that can help protect the
body during the ageing process. The team developed a method of analysing genes in multiple
ageing tissue types in both animals and humans. The analysis, which included more than
five million gene measurements, highlighted the mechanisms used by the body to protect
against cellular changes with age that can result in conditions such as muscle
degeneration and cognitive ageing. The new method could help further understanding into
anti-ageing interventions by identifying genes that indicate biological changes as a
result of ageing. Research has suggested that some genes respond to age-related conditions
by increasing key protein levels, allowing the body to manage the ageing process more
effectively. Dr Joao Pedro Magalhaes, from the University's School of Biological Sciences,
explains: "We developed a new algorithm to analyse microarray data of genes from
different species, and combined data from multiple studies to obtain a picture of how
genes respond to ageing in a whole organism. This method is similar to the way scientists
study the molecular characteristics of cancer, but it is the first time it has been used
to research ageing.
New insight into Rett syndrome
severity
A research collaboration between Australia
and Israel has identified a genetic variation that influences the severity of symptoms in
Rett syndrome. The finding is published in the latest edition of the international journal
Neurology. Dr Helen Leonard, who heads the Australian Rett Syndrome Study at the Telethon
Institute for Child Health Research, said the finding was exciting in that it identifies a
potential new target for treatment of the debilitating neurological disorder. "We
know that there is a wide range in the onset and severity of symptoms in patients with
Rett syndrome but it has been difficult to give families a firm idea of how the disorder
would progress," Dr Leonard said. "This information is potentially helpful in
predicting the clinical progression, but importantly, gives us another area to explore for
potential therapies." In the study, clinical information and DNA samples were
gathered from 125 patients from the Australian Rett Syndrome Database and an Israeli
cohort coordinated by Dr Bruria Ben Zeev at the Safra Pediatric Hospital, Sheba Medical
Centre, Sackler School of Medicine, Tel Aviv. The genetic testing was undertaken by
Professor John Christodoulou, from the NSW Centre for Rett Syndrome Research at the
Children's Hospital at Westmead in Sydney and Dr Eva Gak from the Sagol Neuroscience
Center at the Sheba Medical Centre. Professor Christodoulou said while it has been
established that Rett syndrome is caused by mutations in the MECP2 gene, these new
findings have established a correlation between the severity of clinical symptoms and a
common brain-derived neurotrophic factor (BDNF) polymorphism. "Those patients with
the normal BDNF genetic variant had less severe symptoms, with later onset and frequency
of seizures," Dr Christodoulou said.
Vegan Buddhist nuns have same bone
density as non-vegetarians
A study comparing the bone health of 105
post-menopausal vegan Buddhist nuns and 105 non-vegetarian women, matched in every other
physical respect, has produced a surprising result. Their bone density was identical. The
study was led by Professor Tuan Nguyen from Sydneys Garvan Institute of Medical
Research. He collaborated with Dr Ho-Pham Thuc Lan from the Pham Ngoc Thach Medical
University in Ho Chi Minh City,Vietnam. Their findings are now published online in
Osteoporosis International. "For the 5% of people in Western countries who choose to
be vegetarians, this is very good news," said Professor Nguyen. "Even vegans,
who eat only plant-based foods, appear to have bones as healthy as everyone else."
"Bone health in vegetarians, particularly vegans, has been a concern for some time,
because as a group they tend to have a lower protein and calcium intake than the
population at large."
Breakfast choices impact hunger and
calorie consumption throughout day
New studies presented this week at
Experimental Biology 2009 enhance the growing body of evidence supporting the nutritional
benefits of eggs. Research presented at the meeting demonstrates that choosing eggs for
breakfast can help adults manage hunger while reducing calorie consumption throughout the
day. Additional research shows that teens who choose a protein-rich breakfast are less
hungry and eat fewer calories at lunch.
USC researchers develop new drug to
target tumor cells and blood vessels
Researchers at the University of Southern
California have identified a new drug compound that appears to target tumor cells and
surrounding blood vessels without the negative side effects typically associated with
Cox-2 inhibitors. The compound 2.5-dimethyl-celecoxib (DMC) appears to have a strong
anti-tumor effect while also attacking the vasculature that provides the blood supply
necessary for tumor growth, according to data presented at the AACR 100th Annual Meeting
2009. The findings were presented at a 1 p.m. news conference on Sunday, April 19.
"If left behind, the blood vessels within the tumor will help the tumor cells to
survive and re-grow," says Florence M. Hofman, Ph.D., professor of pathology at the
Keck School of Medicine of USC. "We believe that DMC will be particularly useful for
treating brain tumors such as gliomas, which are highly vascular. It also appears very
promising for long-term treatment because it does not have the negative cardiovascular
effects associated with Cox-2 inhibitors." Cox-2 inhibitors are most commonly used as
anti-inflammatory drugs and have been shown to be effective in treating certain kinds of
cancer. However, long-term use has also been associated with increased risk of heart
attack and stroke, Hofman explains. DMC, however, retains anti-tumor activity without
inhibition of Cox-2 and the associated increased risk of cardiovascular complications.
Hofman and colleagues from the Keck School of Medicine tested the effectiveness of the DMC
compound by isolating endothelial cellsthe cells that line the interior surface of
blood vesselsfrom human nonmalignant brain and glioma tissues and treating them with
DMC.
Autopilot Guides Proteins in Brain
Proteins go everywhere in the cell and do
all sorts of work, but a fundamental question has eluded biologists: How do the proteins
know where to go? "Theres no little man sitting there, putting the protein in
the right place," said Don Arnold, a molecular and computational biologist at USC
College. "Proteins have to have in them encoded information that tells them where to
go in the cell." In a study appearing online this week in Nature Neuroscience, Arnold
and collaborators solve the mystery for key proteins in the brain. Neurons have separate
structures for receiving signals (dendrites) and for sending them (axons). The electrical
properties of each depend on different proteins. But the proteins travel in bubbles, or
vesicles, powered by motors known as kinesins that travel along tiny molecular paths.
Even though the paths point to both axons
and dendrites, dendritic proteins end up in dendrites, and axonal proteins go to the
axons. How? Arnolds group discovered a crude but effective sorting mechanism. At
first, kinesins blindly carry both types of proteins towards the axon. However, dendritic
proteins enable the vesicles transporting them to bind to a second motor, known as myosin,
that literally walks them back into the dendrite. This filter ensures that only axonal
proteins make it into the axon. The others are caught by the second motor and diverted to
the dendrite. "This mechanism fishes these things out of the axon," Arnold said.
Brain metastases hijack
neuron-supporting cells to resist chemotherapy
Cancer that spreads to other organs finds a
particularly inviting hideout in the brain, where these metastases are usually far harder
to treat than they are in other locations. Two researchers from The University of Texas M.
D. Anderson Cancer Center discussed ways to more successfully target these tumors in their
"sanctuary" at the American Association for Cancer Research 100th Annual Meeting
2009 in Denver. Professor of Cancer Biology Isaiah J. Fidler, D.V.M., Ph.D., presented a
novel theory about why brain metastases are resistant to chemotherapy. "Astrocytes
are spider-like cells that normally play the important role of providing oxygen and
nutrients to neurons, and protecting neurons from naturally occurring toxins," Fidler
said. "We show that brain metastases subvert astrocytes, tricking them into
protecting the tumors, and that this is the important factor in resistance to
chemotherapy." Professor and Chair of Neurosurgery Raymond Sawaya, M.D., reviewed
when and how to conduct surgery to remove metastatic tumors, including evidence that
removing a tumor piecemeal raises the risk of cancer irretrievably spreading to the spinal
fluid. Fidler and Sawaya were among five speakers at "Invading the Sanctuary: New
approaches to Brain Metastasis." Metastatic cancer causes the vast majority of cancer
deaths. There are more than 100,000 new cases of metastatic brain cancer each year. By
comparison, primary malignant brain tumors account for about 17,000 new cases annually.
Not all cancers spread to the brain. Sawaya lists lung, breast, melanoma, kidney and colon
cancer as the most common. "It's common for us to operate on patients who no longer
have known disease except for the metastasis in the brain," Sawaya said. Such
patients have a better prognosis than those with heavier tumor burden elsewhere.
An herbal extract inhibits the
development of pancreatic cancer
An herb recently found to kill pancreatic
cancer cells also appears to inhibit development of pancreatic cancer as a result of its
anti-inflammatory properties, according to researchers from the Kimmel Cancer Center at
Jefferson. The data were presented at the AACR 100th Annual Meeting 2009 in Denver.
(Abstract 494) Thymoquinone, the major constituent of the oil extract from a Middle
Eastern herbal seed called Nigella sativa, exhibited anti-inflammatory properties that
reduced the release of inflammatory mediators in pancreatic cancer cells, according to
Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at the Jefferson Medical College
of Thomas Jefferson University and a member of the Jefferson Pancreatic, Biliary &
Related Cancers Center. Nigella sativa seeds and oil are used in traditional medicine by
many Middle Eastern and Asian countries. It helps treat a broad array of diseases,
including some immune and inflammatory disorders, Dr. Arafat said. Previous studies have
also shown it to have anti-cancer effects on prostate and colon cancers. Based upon their
previously published findings that thymoquinone inhibits histone deacetylases (HDACs), Dr.
Arafat and her colleagues compared the anti-inflammatory properties of thymoquinone and
trichostatin A, an HDAC inhibitor that has previously shown to ameliorate
inflammation-associated cancers. The researchers used pancreatic ductal adenocarcinoma
(PDA) cells, some of which were pretreated with the cytokine TNF-alpha to induce
inflammation. Thymoquinone almost completely abolished the expression of several
inflammatory cytokines, including TNF-alpha, interleukin-1beta, interleukin-8, Cox-2 and
MCP-1, an effect that was more superior to the effect of trichostatin A. The herb
also inhibited the activation and synthesis of NF-kappaB, a transcription factor that has
been implicated in inflammation-associated cancer. Activation of NF-kappaB has been
observed in pancreatic cancer and may be a factor in pancreatic cancer's resistance to
chemotherapeutic agents. When animal models of pancreatic cancer were treated with
thymoquinone, 67 percent of the tumors were significantly shrunken, and the levels of
proinflammatory cytokines in the tumors were significantly reduced.
LSUHSC research shows fish oil
protects against diseases like Parkinson's
Dr. Nicolas Bazan, Director of the
Neuroscience Center of Excellence, Boyd Professor, and Ernest C. and Yvette C. Villere
Chair of Retinal Degenerative Diseases Research at LSU Health Sciences Center New Orleans,
will present new research findings showing that an omega three fatty acid in the diet
protects brain cells by preventing the misfolding of a protein resulting from a gene
mutation in neurodegenerative diseases like Parkinson's and Huntington's. He will present
these findings for the first time on Sunday, April 19, 2009 at 10:30 a.m. at the Ernest N.
Morial Convention Center, Nouvelle C Room, at the American Society for Nutrition,
Experimental Biology 2009 Annual Meeting. With funding from the National Eye Institute of
the National Institutes of Health, Dr. Bazan and his colleagues developed a cell model
with a mutation of the Ataxin-1 gene. The defective Ataxin-1 gene induces the misfolding
of the protein produced by the gene. These misshapened proteins cannot be properly
processed by the cell machinery, resulting in tangled clumps of toxic protein that
eventually kill the cell. Spinocerebellar Ataxia, a disabling disorder that affects
speech, eye movement, and hand coordination at early ages of life, is one disorder
resulting from the Ataxin-1 misfolding defect. The research team led by Dr. Bazan found
that the omega three fatty acid, docosahexaenoic acid (DHA), protects cells from this
defect. Dr. Bazan's laboratory discovered earlier that neuroprotectin D1 (NPD1), a
naturally-occurring molecule in the human brain that is derived from DHA also promotes
brain cell survival. In this system NPD1 is capable of rescue the dying cells with the
pathological type of Ataxin-1, keeping their integrity intact. "These experiments
provide proof of principle that neuroprotectin D1 can be applied therapeutically to combat
various neurodegenerative diseases," says Dr. Bazan. "Furthermore, this study
provides the basis of new therapeutic approaches to manipulate retinal pigment epithelial
cells to be used as a source of NPD1 to treat patients with disorders characterized by
this mutation like Parkinson's, Retinitis Pigmentosa and some forms of Alzheimer's
Disease."
Clouds - Lighter than air but laden
with lead
By sampling clouds -- and making their own
-- researchers have shown for the first time a direct relation between lead in the sky and
the formation of ice crystals that foster clouds. The results suggest that lead generated
by human activities causes clouds to form at warmer temperatures and with less water. This
could alter the pattern of both rain and snow in a warmer world. The lead-laden clouds
come with a silver lining, however. Under some conditions, these clouds let more of the
earth's heat waft back into space, cooling the world slightly. Atmospheric lead primarily
comes from human sources such as coal. The international team of researchers reported
their results in the May issue of Nature Geoscience. The collaboration included
researchers from institutions in the United States, Switzerland and Germany. "We know
that the vast majority of lead in the atmosphere comes from man-made sources," said
atmospheric chemist Dan Cziczo of the Department of Energy's Pacific Northwest National
Laboratory and study author. "And now we show that the lead is changing the
properties of clouds and therefore the balance of the sun's energy that affects our
atmosphere."
Urine test may determine if a
smoker is at risk for lung cancer
Researchers may have uncovered why lung
cancer afflicts some smokers and not others, according to data presented at the American
Association for Cancer Research 100th Annual Meeting 2009. "A history of smoking has
always been thought of as a predictor of lung cancer, but it is actually not very
accurate," said Jian-Min Yuan, Ph.D., M.D., associate professor of public health at
the University of Minnesota. "Smoking absolutely increases your risk, but why it does
so in some people but not others is a big question." Yuan and colleagues hypothesized
that the presence of the metabolite NNAL in a patient's urine might predict risk of lung
cancer. This metabolite has been shown to induce lung cancer in laboratory animals, but
the effect in humans had not yet been studied. Researchers collected data from 18,244 men
enrolled in the Shanghai Cohort Study and 63,257 men and women from the Singapore Chinese
Health Study. In addition to in-person interviews to assess levels of cigarette smoking,
dietary and other lifestyle factors, researchers collected blood and urine samples from
more than 50,000 patients. To evaluate the impact of NNAL, researchers identified 246
current smokers who later developed lung cancer and 245 smokers who did not develop lung
cancer during the 10-year period following initial interview and collection of urine
samples. Levels of NNAL in the urine were divided into three groups. Compared to those
with the lowest levels, patients with a mid-range level of NNAL had a 43 percent increased
risk of lung cancer, while those at the highest level had a more than two-fold increased
risk of lung cancer after taking into account the effect of number of cigarettes per day,
number of years of smoking, and urinary levels of cotinine on lung cancer risk. Levels of
nicotine in the urine were also calculated. Those with the highest levels of nicotine and
NNAL had an 8.5-fold increase in the risk of lung cancer compared with smokers who had the
lowest levels after accounting for smoking history. "Smoking leads to lung
cancer, but there are about 60 possible carcinogens in tobacco smoke, and the more
accurately we can identify the culprit, the better we will become at predicting
risk," said Yuan.
Is metabolic character different
between men and women with gallstone disease?
There are a cluster of metabolic syndrome,
that include obesity, high level of fasting plasma glucose, hypertriglyceridemia and
hypertension, which is closely associated with the increased morbidity and mortality
caused by several of the most common diseases including diabetes, hypertension,
cardiovascular diseases, cancer and gallstone disease. However, there are regional and
ethic variables in incidence and metabolic risk factors of gallstone disease. No study
explores it in china has been reported. A research article to be published on April 21,
2009 in the World Journal of Gastroenterology addresses this question. The research team
led by Professor Tang from Center of Infectious Diseases, Division of Molecular Biology of
Infectious Diseases, National Key Laboratory of Biotherapy (Sichuan University), West
China Hospital of Sichuan University carried out a study in a check-up unit in a
university hospital in Chengdu city to study the incidence and metabolic risk factor of
gallstone disease. As various researches indicated old age and female sex are susceptible
to gallstone disease, the article investigate the relationship of metabolic disorders and
gallstone disease. The prevalence of gallstone disease among the study subjects was 10.7%
. The reported prevalence of gallstone disease is approximately 3.6% in Japan and 4.3-5.0%
in Taiwan. The present study, in accordance with reports from western countries and other
regions of Asia, showed that an older age, which may lead to exposure to many other risk
factors, and female sex, which may have increasing risk of biliary cholesterol secretion
causing cholesterol super saturation of bile by pregnancy and estrogen, are significant
risk factors for gallstone disease. The present analyses showed a positive association
between DM and gallstone disease in men but not in women and hypertriglyceridemia or
obesity only showed a positive association with gallstone disease in women. There were
disparate findings about DM, hypertriglyceridemia and obesity in different sexes with
gallstone. These results demonstrate men have different metabolic character from women in
gallstone disease patients, which may provide more information for investigating the true
pathological mechanism of gallstone disease.
What is the effect of tea
polyphenols on hepatic drug metabolizing enzymes?
Paracetamol is one of the most widely used,
studied, and arguably the most notorious hepatotoxic drugs, which is safe at therapeutic
doses but causes liver failure when overdosed. When administered at normal doses,
paracetamol is metabolized extensively by conjugation with sulphate and glucuronic acid.
Exposure to high doses of paracetamol results in increased levels of
N-acetyl-p-benzo-quinoneimine (NAPQI), a highly electrophilic metabolite that is
considered to be responsible for triggering the ensuing liver damage. The research, lead
by Dr. Sun and his colleagues in Dalian Medical University, has recently been published on
April 21,2009 in World Journal of Gastroenterology, investigated the effect of tea
polyphenols (TPs) on paracetamol-induced hepatotoxicity. TPs are a large and diverse class
of compounds extracted from tea. Recent studies indicate that TPs prevent from oxidative
stress-related diseases including cancer, cardiovascular diseases, degenerative diseases
and other bioactive properties. In recent years there has been a mounting interest in
understanding the metabolic benefits of TPs. Liver is the main organ responsible for the
metabolism of TPs. And some works have been done in the field of TPs modulated or
interacted with drug metabolizing enzymes. However, until now, no one could give a clear
explanation about this. Cytochrome P450 (CYP450) enzymes play a pivotal role not only in
the metabolism of xenobiotics, and both induction and suppression of several CYP450s may
lead to the cellular oxidative stress and tissue injury in response to xenobiotics. Early
investigations identified the important roles of CYP2E1, CYP1A2 and intracellular GSH in
paracetamol induced hepatotoxicity. But the effect of TPs on paracetamol-induced
hepatotoxicity remain unclear. This research gave a clear explanation of TPs' effect on
hepatic CYP450 along with CYP2E1 and CYP1A2 expression at both protein and mRNA levels.
The results showed that the contents of hepatic CYP450 and CYPb5 were dose-dependently
decreased by TPs. Also, TPs reduced CYP2E1 and CYP1A2 expression at both protein and mRNA
levels dose dependently, indicating that TPs possessed potential hepatoprotective
properties and this effect was closely related with their suppression on CYP450
expression. These results provided new information of TPs about their metabolism and the
effect of TPs on hepatic drug metabolizing enzyme. This will be important in developing
clinically safe and efficient medications related to TPs.
Genetic source of rare childhood
cancer found; gene is implicated in other cancers
The search for the cause of an inherited
form of a rare, aggressive childhood lung cancer has uncovered important information about
how the cancer develops and potentially sheds light on the development of other cancers.
The finding by researchers at Washington University School of Medicine in St. Louis,
Children's National Medical Center in Washington, D.C., the International Pleuropulmonary
Blastoma Registry at Children's Hospitals and Clinics of Minnesota, and other
collaborating institutions adds the final link to the chain connecting the gene DICER1 to
cancer development something that had been suspected but until now not definitively
demonstrated. The results were presented April 19, 2009, at the 100th Annual Meeting of
the American Association of Cancer Research in Denver. The study shows that some children
with the rare cancer pleuropulmonary blastoma (PPB) are born with a deleterious mutation
in DICER1, a master controller gene that helps regulate the expression of other genes. The
children studied came from families with a history of PPB or related disorders. "PPB
is the first malignancy found to be directly associated with inherited DICER1 mutations,
making the cancer an important model for understanding how mutations and loss of DICER1
function lead to cancer," says lead author D. Ashley Hill, M.D., chief of pathology
at Children's National Medical Center. "Additionally, we now believe that PPB tumors
arise from an unusual mechanism in which cells carrying mutations induce nearby cells to
become cancerous without becoming cancerous themselves." Hill was principal
investigator of the study, which began while she was on the Washington University faculty.
Instead of fighting breast cancer,
immune cell promotes its spread
Researchers at the UC San Diego School of
Medicine and the Moores UCSD Cancer Center have new evidence that a type of immune system
cell thought to be part of the first line of defense against breast cancer may also help
promote its spread. They have found that when these cells, known as lymphocytes, make an
inflammatory protein called RANKL (RANK ligand), breast cancer is more likely to spread to
the lungs. They have also shown that blocking a cascade of cellular signals that follow
RANKL's docking to its receptor (RANK) on tumor cells can halt cancer progression, or
metastasis, and may be a possible target for drug therapy. The scientists, led by first
author Wei Tan, PhD, a postdoctoral fellow in the Department of Pharmacology at the UC San
Diego School of Medicine and Michael Karin, PhD, professor of pharmacology in UCSD's
Laboratory of Gene Regulation and Signal Transduction, say that the findings establish
RANKL as a potential marker that can be used to help determine breast cancer prognosis and
adds further proof to the potentially important role of inflammation in cancer development
and spread. They reported their findings April 22, 2009 at the AACR 100th Annual Meeting
2009 in Denver. According to Tan, the role of lymphocytes in breast cancer progression has
been controversial for the last 20 years. Such cells are supposed to detect and eliminate
cancer cells, but paradoxically, the infiltration of lymphocytes such as B cells and T
cells into breast cancer is sometimes an indicator of poor prognosis, including cancer
recurrence and metastasis. RANKL has been shown in previous studies to be an important
inflammatory protein that can lead to bone loss by activating cells that help break down
bone. Along with another protein, IKK alpha, it has been implicated both in tumor
formation and metastasis. The researchers created two types of mice that developed breast
tumors. One group had lymphocytes in the tumors and expressed RANKL while the other group
did not. They found that the group lacking RANKL had significantly fewer lung metastases
than those mice with RANKL. They then took tumor cells from both types of mice and
injected them into mice with the same genetic background to avoid rejection and monitored
the ability of the mice to form tumors and metastases to the lung. The researchers didn't
find any lung tumor metastases in mice without lymphocytes. Yet, when RANKL was injected
into the animals, the same potential for the cancer to spread was restored, indicating
that the lymphocytes, which make RANKL, are critically important to the process.
"Without lymphocytes, there is no metastasis," said Tan. "If we treat the
mice with RANK ligand, there are metastases, which indicate that RANK ligand can
compensate for the function of lymphocytes." The study establishes the role of
RANKL-expressing lymphocytes as a promoting factor in breast cancer metastasis and
provides a potentially good marker for breast cancer prognosis, the researchers said.
Binge Drinking May Hamper
Information Relay System in Teen Brain
A study of adolescent binge drinkers has
found that even relatively infrequent exposure to large amounts of alcohol during the teen
years may compromise the integrity of the brains white matter, which is critical for
the efficient relay of information within the brain. The preliminary findings to be
published online in advance of the July issue of the journal Alcoholism: Clinical &
Experimental Research indicate that binge drinking may be detrimental to the
developing adolescent brain. Heavy episodic or binge drinking is common among
adolescents, with 55% of high-school seniors reporting having gotten drunk, and a quarter
of them reporting having consumed five or more drinks in a row during the previous two
weeks. Because the brain is still developing during adolescence, there has been
concern that it may be more vulnerable to high doses of alcohol, said Susan F.
Tapert, PhD, director of Substance Abuse/Mental Illness at the VA San Diego Healthcare
System and associate professor of psychiatry at the University of California, San Diego
School of Medicine. This study showed that teens with histories of binge drinking
episodes have lower coherence of white matter fibers in a variety of brain regions.
White matter is the part of the brain made up of the axons of neurons
long filaments that extend from the cell bodies and carry the electrical signals that
relay messages between neurons. The area appears white because of the axons
protective myelin covering. Researchers know that the integrity of the brains white
matter is compromised in adult alcoholics, but it is unclear when during the course of
drinking white matter abnormalities begin to manifest themselves. However, white matter
has been shown to continue developing throughout young adulthood.
Researchers identify missing target
for calcium signaling
An international study led by Ohio State
University neuroscience researchers describes one of the missing triggers that controls
calcium inside cells, a process important for muscle contraction, nerve-cell transmission,
insulin release and other essential functions. The research is being posted online April
22 in the journal Nature. The researchers believe the findings will enhance the
understanding of how calcium signals are regulated in cells and shed light on new ways to
treat many diseases, including cardiovascular diseases, immune diseases, metabolic
diseases, cancer, and brain disorders. The study found that molecular structures called
two-pore channels (TPCs) cause the release of calcium when stimulated by a substance
called NAADP. The researchers also show that TPCs are located in the membranes of cell
components called lysosomes and endosomes. These are mobile structures within cells that
were not previously thought to be sites of calcium release. Furthermore, the discharge of
calcium from these structures can prompt much larger releases from stores located on the
large and elaborate membrane network called the endoplasmic reticulum. "Our study
discovered one of the missing targets for calcium signaling," says Michael Xi Zhu,
associate professor of neuroscience and a researcher with Ohio State's Center for
Molecular Neurobiology. "It also nails down that NAADP receptors are located on
lysosomes and endosomes, which should change people's views of calcium signaling.
"It's as if we now understand that cells have not only a primary battery for calcium
but other batteries in different places."
Genetics can mediate vulnerability
to alcohol's effects during pregnancy
Drinking alcohol during pregnancy can lead
to teratogenesis, the development of embryonic defects. The estimated incidence of Fetal
Alcohol Spectrum Disorders (FASD), referring to a wide array of alcohol-exposure effects,
is approximately one percent of live births in the US. Yet not all women who drink during
pregnancy give birth to children with observable deficits. A mouse study has found that
genetics may help to explain alcohol-related susceptibility and resistance. Results will
be published in the July issue of Alcoholism: Clinical & Experimental Research and are
currently available at Early View. "Alcohol-related deficits include pre and/or
postnatal growth retardation, craniofacial anomalies, central nervous system dysfunction,
hand or finger malformations, a number of different skeletal malformations, and anomalies
in a number of different organ systems, including the brain, eyes, and kidney," said
Chris Downing, a research associate at the University of Colorado and corresponding author
for the study. "Some women who drink during pregnancy don't give birth to children
with any of these observable deficits, but later on their children develop a number of
behavioral deficits including hyperactivity, attention deficits, learning problems, and
deficits in impulse control," Downing added. "It is thought that these
behavioral deficits are due to brain damage as result of in utero ethanol exposure, but
correlating specific behavioral deficits with damage to specific brain areas is a work in
progress. In addition, some women who drink during pregnancy have 'normal' children with
no obvious deficits." Downing said that many factors have been shown to play a role
in the development of FASD, including the amount, timing and pattern of maternal alcohol
consumption, maternal age and parity, maternal ethnicity and socioeconomic status,
cultural factors, maternal smoking and other drug abuse, and maternal diet/nutrition. In
addition, he said, studies with humans and mice have shown that both maternal and fetal
genotypes in conjunction with the environment play a role in susceptibility
and resistance to the detrimental effects of in utero alcohol exposure.
Humanin peptide linked to neuronal
cell survival and regulation of glucose metabolism
Recent studies have shown that the
mitochondrial peptide Humanin (HN) protects against neuronal cell death such as happens in
Alzheimer's disease. Now, in a study presented April 22 at Experimental Biology 2009 in
New Orleans, Dr. Nir Barzilai reports that a small infusion of HN is the most potent
regulator of insulin metabolism that his research team has ever seen, significantly
improving overall insulin sensitivity and sharply decreasing the glucose levels of
diabetic rats. The finding is the first evidence of a role for HN in glucose metabolism
and provides new insight into how this metabolism may be involved in the development of
seemingly diverse age-related diseases such as Type 2 Diabetes Mellitus and Alzheimer's.
The finding also provides support for the growing understanding that the brain (not just
the pancreas, liver and other peripheral organs) is heavily involved in glucose
metabolism. Furthermore, says Dr. Barzilai, the Ingeborg and Ira Leon Rennert Chair of
Aging Research and Director of the Institute for Aging Research at the Albert Einstein
College of Medicine, the power of HN on insulin action suggests a new therapeutic approach
to diabetes. Further understanding of how HN interactions with the growth
hormone/insulin-like growth factor system may also lead to strategies to protect against
age-related diseases including Alzheimer's.
Test for hormones in blood not
reflective of hormones in breast tissue; breast cancer risk
Many studies determine hormone levels in
the blood as a marker of breast cancer risk. But it hasn't been known whether these blood
tests reflect what is happening in the breast tissue, where certain hormones fuel cancer.
Researchers at Georgetown University Medical Center's (GUMC) Lombardi Comprehensive Cancer
Center found that measuring the levels of four hormones in blood known to be linked to
breast cancer doesn't necessarily reflect the levels of these hormones in the breast
tissue itself. In fact, the scientists say that blood tests used in research studies that
measure these hormones could give a false impression of both the real breast cancer risk
women face, and an imprecise picture of how these hormones affect breast cancer
development. The findings are being presented at the Annual Meeting of the American
Association for Cancer Research. "We know from this study that measuring the hormones
in a patient's blood is not sufficient but that is how many research studies looking at
breast cancer risk are being conducted," says the study's lead author, Adana Llanos,
a graduate student in genetics at GUMC. "Understanding how cancers develop in breast
tissue is the key to prevention, and we need to understand how these hormones affect
breast tissue." The research team, led by Llanos and under the guidance of senior
investigator, Peter G. Shields, MD, head of Lombardi's Cancer Genetics and Epidemiology
Program, did something that has not been done before: They tested normal breast tissue for
the levels of IGF-1, IGFBP-3, adiponectin, and leptin. High levels of IGF-1 has been
linked to breast cancer development, while low levels of IGFBP-3 is linked to increased
risk. High levels of adiponectin and leptin are both related to obesity, which is, in
itself, a risk factor for breast cancer. "By understanding these hormones in the
normal breast environment, we will have some insight into how early changes in the breast
lead to breast cancer," Llanos says. The researchers asked 15 women who were
undergoing breast reduction surgery to participate in the study, and then collected three
samples of discarded tissue from each breast, as well as blood, and extensive
epidemiological data. They first assessed whether levels of these hormones were the same
in each of the three tissue samples taken from the women, which represented different
areas of the breast. "We found that the hormones were distributed in the same way
across the breast, which is a good thing to know because it means that a tissue biopsy
taken from one part of the breast will likely represent the breast as a whole," says
Llanos. They then tested the blood to see if levels of the hormones matched those found in
the breast tissue, and found that leptin, adiponectin, and IGFBP-3 correlated, whereas
IGF-1 did not. But even that may be misleading, Llanos says, because hormone levels may
differ between a woman's two breasts. "Breast cancer usually develops in a single
breast, so it is not clear that looking at these hormones in the blood is
sufficient," she says.
Test for Hormones in the Blood Not
Reflective of Hormones in Breast Tissue; Breast Cancer Risk
Many studies determine hormone levels in
the blood as a marker of breast cancer risk. But it hasnt been known whether these
blood tests reflect what is happening in the breast tissue, where certain hormones fuel
cancer. Researchers at Georgetown University Medical Centers (GUMC) Lombardi
Comprehensive Cancer Center found that measuring the levels of four hormones in blood
known to be linked to breast cancer doesnt necessarily reflect the levels of these
hormones in the breast tissue itself. In fact, the scientists say that blood tests used in
research studies that measure these hormones could give a false impression of both the
real breast cancer risk women face, and an imprecise picture of how these hormones affect
breast cancer development. The findings are being presented at the Annual Meeting of the
American Association for Cancer Research. We know from this study that measuring the
hormones in a patients blood is not sufficient but that is how many research studies
looking at breast cancer risk are being conducted, says the studys lead
author, Adana Llanos, a graduate student in genetics at GUMC. Understanding how
cancers develop in breast tissue is the key to prevention, and we need to understand how
these hormones affect breast tissue. The research team, led by Llanos and under the
guidance of senior investigator, Peter G. Shields, MD, head of Lombardis Cancer
Genetics and Epidemiology Program, did something that has not been done before: They
tested normal breast tissue for the levels of IGF-1, IGFBP-3, adiponectin, and leptin.
High levels of IGF-1 has been linked to breast cancer development, while low levels of
IGFBP-3 is linked to increased risk. High levels of adiponectin and leptin are both
related to obesity, which is, in itself, a risk factor for breast cancer.
More evidence that humans continue
to upset nature
Dartmouth researchers have determined that
the presence of the rare element osmium is on the rise globally. They trace this increase
to the consumption of refined platinum, the primary ingredient in catalytic converters,
the equipment commonly installed in cars to reduce smog. A volatile form of osmium is
generated during platinum refinement and also during the normal operation of cars, and it
gets dispersed globally through the atmosphere. While osmium is found naturally, the
researchers were surprised to discover that most of the osmium in rain and snow, and in
the surface waters of rivers and oceans, is produced during the refining of platinum.
"It's interesting, maybe ironic, that we stopped adding lead to gasoline in the 70s
so that catalytic converters could be introduced to remove smog from car exhaust,"
says Dartmouth Associate Professor of Earth Sciences Mukul Sharma. "Now we learn that
using platinum in the converters is responsible for an increase in osmium. Fortunately,
unlike lead, the concentration of osmium in water is extremely small and may not adversely
affect biology." Sharma worked with Dartmouth Ph.D. student Cynthia Chen and Peter
Sedwick at Old Dominion University. Their study will be published in the online edition of
the Proceedings of the National Academy of Sciences during the week of April 20, 2009. The
research team measured osmium in precipitation in North America, Europe, Asia, and
Antarctica, and in both surface water and deep water from the North Atlantic, Pacific,
Indian, and Antarctic (or Southern) Oceans. Human-made osmium also comes from chromium
smelters, hospital incinerators, and the normal operation of cars, but it's primarily the
industrial extraction and refining of platinum that produces the bulk of the osmium found
in rain and snow. Sharma explains that about 95 percent of the world's platinum comes from
South Africa and Russia where it is roasted at extremely high temperatures during the
extraction and refinement process. The process removes sulfur present in the ore as sulfur
dioxide and, at the same time, releases osmium, which is abundant in the ore.
Study sheds new light on why
breast-fed babies grow more slowly
Breast-fed babies grow more slowly than
formula-fed babies, which is why new growth charts, based solely on the growth patterns of
breast fed babies, are being introduced in the UK in May. This slower pattern of growth in
the first year of life is possibly one reason why breast-fed babies are less likely to
become overweight children later on. A study published on-line today (24 April 2009) in
the American Journal of Clinical Nutrition has found evidence that the lower protein
content of breast milk compared to formula milk explains the slower growth rates seen in
breast fed infants. The study was a multi-centre intervention trial in 5 European
countries, co-ordinated by Professor Berthold Koletzko from the University of Munich,
Germany. Over 1000 infants were randomised to receive infant and follow-on formulas with
lower or higher protein content for their first year and were then followed up for 2
years. A group of breast fed infants were also followed up for comparison.
Aston University to explore
anti-oxidant benefits of UK grown rosemary
The benefits of UK grown rosemary are set
to be explored, and with it the potential to create a new genre of renewable bio-based
antioxidants. Polymer scientists at Aston University in Birmingham, UK, have been awarded
a £235,000 grant to develop a range of antioxidants from the active natural ingredients
present in rosemary. Synthetic antioxidants, added to provide stability to products in
areas as diverse as cosmetics, food and drink packaging and car lubricants, help to
prevent or reduce the formation of active chemical species (free-radicals) that are
responsible for the deterioration and breakdown of organic materials. The damaging effects
of free radicals are also often linked to cancer and other degenerative conditions in the
human body. The aim of the research is to replace some of these synthetic antioxidants
with rosemary-derived antioxidants to add a natural and renewable source to products. This
will also help address potential issues relating to safety and toxicity in human-contact
applications. Dr Sahar Al-Malaika, Reader in Chemical Engineering and Applied Chemistry at
Aston, who is a pioneer on the use of vitamin E as an antioxidant in polymers, believes
that this latest research could prove as significant. They are studying UK grown rosemary
in particular, as evidence suggests the plant yields higher levels of antioxidants than
those grown on the continent.
SPEEDY babies a new
behavioural syndrome
Childrens speech and language
disorders caused by unknown factors are common. The disorders vary in type and manifest
themselves differently in different ages. Delayed motor development is widely known to
coexist with speech and language disorders. However, hardly any attention has been paid to
children in whom delayed speech development is associated with learning to walk unassisted
at an early stage. Dr Marja-Leena Haapanen from the Phoniatric Division of the Helsinki
University Central Hospital has studied and described these children and observed a
recurrent pattern in their behavioural phenotype. The children were examined by a
multi-disciplinary research group over an extensive period in time. Usually these
children, known as SPEEDY babies, have good language comprehension skills, but their
speech is very unclear, although they may start speaking early on and can be quite
talkative. In some cases, the speech production is delayed, the child speaks less, and the
speech maybe unclear, especially when speaking long sentences. What makes the childs
speech unintelligible are words and sentences that are produced incorrectly, but each time
in a different way, in addition to consistent sound distortion. Consistent sound
distortions are associated with tongue dysfunction and are manifest in sounds in which the
tip of the tongue is used. SPEEDY babies develop motor skills early, and often start
walking unassisted at ten months. They are often avid runners, climbers and eager to jump
and skip, and all in all, are quite agile and physically active. They are usually in good
physical health, and do not typically suffer from respiratory infections, ear infections
or allergies. The intellectual skills structure is usually divided so that their
vision-based performance is above the average for their age group and better than their
linguistic performance.
Ultrasound Can Help Low-Risk
Patients Avoid Invasive Thyroid Biopsy
The prevalence of benign thyroid nodules is
high and there are certain ultrasound features, suggesting malignancy, that can help
radiologists determine whether or not a biopsy is needed, according to a study performed
at the University of California San Francisco Medical Center, San Francisco, CA. A total
of 245 patients (54 patients with cancer, 191 patients with no cancer) were analyzed.
Our study supports previous data showing that some sonographic features of thyroid
nodules are suggestive of malignant nature and should lead to biopsy, said Dorra
Sellami, MD, lead author of the study. These features include microcalcifications
(which increase the risk of cancer 16 folds), a shape taller than wide (increases the risk
of cancer 3.7 folds) and hypoechogenicity (two-fold increase in risk of cancer). Other
features may suggest that a nodule is benign, such as hyperechogenicity (40% increase in
risk of cancer), she said. Current clinical guidelines recommend biopsy of all
lesions greater than or equal to 10 mm. However, in our study of patients with no thyroid
cancer, 49% had at least one nodule greater than or equal to 10 mm, said Dr.
Sellami. Very few thyroid nodules are obviously malignant or benign. Most thyroid
nodules we see by ultrasound are indeterminate, and in order to rule out cancer, a fine
needle aspiration is often recommended. This results in a ratio of ten benign nodules
sampled for one cancer diagnosed, she said. Our findings will help
radiologists and clinicians determine which nodules are definitely not suspicious and can
be watched. I think that our study is one step toward decreasing the number of invasive
procedures in patients with benign thyroid noduleswhile maintaining the same
vigilance in detecting thyroid cancer in its early stages, said Dr. Sellami.
Even modest exercise can reduce
negative effects of belly fat
A new University of Illinois study suggests
that moderate amounts of exercise alone can reduce the inflammation in visceral
fatbelly fat, if you willthat has been linked with metabolic syndrome, a group
of risk factors that predict heart disease and Type 2 diabetes. "In the study, the
benefits of exercise were apparent, even without a change in diet. We saw improvements in
insulin sensitivity, less fat in the liver, and less inflammation in belly fat," said
Jeffrey Woods, a U of I professor of kinesiology and community health and faculty member
in the U of I Division of Nutritional Sciences and the Integrative Immunology and Behavior
Program. Belly fat is particularly dangerous because it produces inflammatory molecules
that enter the bloodstream and increase the risk of heart disease and diabetes, he said.
"Scientists now know that obesity is associated with a low-grade systemic
inflammation. Obese people have higher levels of circulating inflammatory markers, such as
C-reactive protein (CRP), which are produced and secreted by fat tissue. This inflammation
then triggers the systemic diseases linked with metabolic syndrome, such as Type 2
diabetes and heart disease," he said. In the study, Woods and his colleagues examined
the effects of diet and exercise on the inflammation of visceral fat tissue in mice. A
high-fat diet was first used to induce obesity in the animals. After 6 weeks, mice were
assigned to either a sedentary group, an exercise group, a low-fat diet group, or a group
that combined a low-fat diet with exercise for 6 or 12 weeks so the scientists could
compare the effects in both the short and long term. "The surprise was that the
combination of diet and exercise didn't yield dramatically different and better results
than diet or exercise alone," said Vicki Vieira, the lead author of the study.
Type of vitamin B1 could treat
common cause of blindness
University of Texas Medical Branch at
Galveston researchers have discovered that a form of vitamin B1 could become a new and
effective treatment for one of the world's leading causes of blindness. Scientists believe
that uveitis, an inflammation of the tissue located just below the outer surface of the
eyeball, produces 10 to 15 percent of all cases of blindness in the United States, and
causes even higher rates of blindness globally. The inflammation is normally treated with
antibiotics or steroid eye drops. In a paper appearing in the May issue of the journal
Investigative Ophthalmology and Visual Science, however, the UTMB researchers describe
striking results achieved with benfotiamene, a fat-soluble form of vitamin B1. In their
experiments, they first injected laboratory rats with bacterial toxins that ordinarily
produce a reaction mimicking uveitis. When those rats are fed benfotiamene, they fail to
develop any signs of the inflammatory disorder. "Benfotiamene strongly suppresses
this eye-damaging condition and the biochemical markers we associate with it," said
UTMB associate professor Kota V. Ramana, senior author of the study. "We're
optimistic that this simple supplementation with vitamin B1 has great potential as a new
therapy for this widespread eye disease."
The researchers' data shows benfotiamene works by suppressing the activation of a crucial
signaling molecule called NF-kappa B, which is normally triggered by the stress caused by
infection. Shutting down NF-kappa B, they said, prevents the runaway production of
inflammatory proteins that generates uveitis. Benfotiamene's low cost, rapid absorption by
the body and lack of negative side effects make it an ideal candidate for uveitis
prevention, according to Ramana.
Radiation device in the breast
reduces complications for early stage breast cancer patients
A new study shows that the SAVI
applicator, a small, expandable device inserted inside the breast to deliver partial
breast irradiation, carries a low infection risk, a potential complication of such
devices. The research, led by radiation oncologists and surgeons at the Moores UCSD Cancer
Center and Fort Myers, Florida-based 21st Century Oncology, also indicates that other
complications such as seromas, pockets of fluid that build with the use of internal
radiation devices are unlikely to occur.
That's good news for those women with early-stage breast cancer who opt to have such
devices inserted for their radiation therapy after breast-sparing lumpectomy surgery, said
Cate Yashar, MD, associate professor of radiation oncology at the UC San Diego School of
Medicine and chief of breast and gynecological radiation services at the Moores UCSD
Cancer Center. Their use is increasing, she added, noting that the Moores UCSD Cancer
Center was one of the first medical facilities in the country to offer SAVI. SAVI, which
consists of flexible catheters through which radiation is given, provides customized
radiation therapy and minimizes exposure to healthy tissue after a woman has undergone a
lumpectomy to remove a cancerous tumor. Radiation specialists sometimes decide to give
women internal radiation a process called brachytherapy with the goal of
giving concentrated doses of radiation to areas of concern while avoiding healthy tissue.
New mediator of smoking recruits
Current research suggests that smoking
increases the production of osteopontin in the lungs, which contributes to the development
of smoking-related lung disease. The related report by Prasse et al, "Essential role
of osteopontin in smoking-related interstitial lung diseases," appears in the May
2009 issue of The American Journal of Pathology.
Nearly one billion people worldwide smoke tobacco products. Long-term exposure to
compounds found in smoke can lead to both cardiovascular and lung disease. Although lung
exposure to cigarette smoke leads to immune cell recruitment and tissue fibrosis, how
cigarette smoke causes these changes is largely unknown. To determine if osteopontin, a
molecule that attracts immune cells, mediates cell recruitment in smokers, Prasse et al
compared osteopontin levels from smokers with different types of lung diseases, healthy
smokers, and healthy non-smokers. They found high levels of osteopontin expression in
patients with interstitial lung disease, whereas healthy smokers had lower levels, and
healthy non-smokers produced no osteopontin. Osteopontin expression could be stimulated
directly by nicotine treatment. In addition, expressing osteopontin in rat lung resulted
in recruitment of immune cells, resulting in symptoms similar to smoking-related
interstitial lung diseases. These results indicate that osteopontin may be pathogenic in
smoking-initiated lung disease.
Stopping Autoimmunity Before It
Strikes
Current research describes a new method to
track the development of autoimmune diseases before the onset of symptoms. The related
report by Zangani et al, Tracking early autoimmune disease by bioluminescent imaging
of NF-?B activation reveals pathology in multiple organ systems, appears in the
April 2009 issue of The American Journal of Pathology. Autoimmune diseases such as lupus,
multiple sclerosis, rheumatoid arthritis and diabetes are caused when the immune system
attacks
the bodys own cells. Normally, immune cells are prevented from attacking normal
cells; however, in patients with autoimmune disease, this tolerance is lost.
The immediate causes of autoimmune diseases remain unknown, partially due to the inability
to detect disease before the onset of symptoms. Early detection of autoimmune disease is
critical for assessing new treatments.