News 25 march 2009
A new approach to prostate cancer
detection
On Friday 20 March, US researcher Dr. Chris
Beecher from the University of Michigan gave a well attended lecture about sarcosine, an
N-methyl derivative of the amino acid glycine, at the 24th Annual EAU Congress in
Stockholm, Sweden. Dr Beecher is a colleague of lead author Dr. Arun Sreekumar. The
research of Sreekumar, Beecher and their team looked at more than 1,000 small molecules in
tissues associated with prostate cancer. These findings suggest that not only is sarcosine
a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant
properties. Sreekumar´s publication in Nature (457, 12 February 2009: 910-914) has
attracted a lot of scientific and also popular attention. The EAU Scientific Congress
Office inserted a special breaking news session in the congress programme in order to
present the most updated scientific information in Stockholm. Sarcosine may distinguish
slow-growing prostate cancers from those likely to spread and become lethal. Conveniently,
sarcosine can be identified in urine, a less invasive test than the blood analysis needed
for the standard prostate-specific antigen (PSA), a protein produced by the cells of the
prostate gland. PSA is present in small quantities in the serum of healthy men, and is
often elevated in the presence of prostate cancer. Quite often men have PSA scores that
fall into a grey area. Therefore, invasive biopsy is needed to clarify a diagnosis.
HIV-1 protease inhibitor induced
oxidative stress in pancreatic B-cells
Researchers at the Tulane University School
of Medicine, New Orleans, Louisiana have discovered that the HIV-1 protease inhibitors
(PIs), such as nelfinavir included in highly active antiretroviral therapy (HAART) regimen
for the treatment of HIV-1 patients, induce deleterious effects on insulin secretion
mediated through the oxidative stress pathway. They report a significant decrease in the
levels of the antioxidants, cytosolic superoxide dismutase (Cu/Zn SOD) and glutathione,
whereas mitochondrial SOD levels remained unaffected in pancreatic beta-cells (INS-1
cells) exposed to nelfinavir. However, the mitochondrial uncoupling protein (UCP2) levels
were up-regulated during nelfinavir induced oxidative stress and directly affected the ATP
levels in these cells. A significant decrease in ATP production was also observed which
may account for the decrease in glucose stimulated insulin secretion upon nelfinavir
treatment. This study appears in the April 2009 issue of Experimental Biology and
Medicine. Although insulin resistance has been clinically observed in HIV-1 patients
receiving HAART regimen, the molecular mechanisms of this metabolic abnormality have not
been delineated.
New drug agent knocks out multiple
enzymes in cancer pathway
A team of 24 researchers from the U.S.,
Europe, Taiwan and Japan and led by University of Illinois scientists has engineered a new
anti-cancer agent that is about 200 times more active in killing tumor cells than similar
drugs used in recent clinical trials.The study appears this week in the Journal of the
American Chemical Society. The new agent belongs to a class of drugs called
bisphosphonates. These compounds were originally developed to treat osteoporosis and other
bone diseases, but were recently found to also have potent anti-cancer and immune boosting
properties. Drug developers have tried for years to design drugs to inhibit cell survival
pathways in tumor cells, focusing on a protein called Ras since nearly a third of all
human cancers involve a mutation in the Ras gene that causes cell signaling to go awry.
These efforts have met with limited success. Bisphosphonates act on other enzymes, called
FPPS and GGPPS, which are upstream of Ras in the cell survival pathway. Inhibiting these
enzymes appears to be a more effective strategy for killing cancer cells. When used in
combination with hormone therapy in a recent clinical trial, the bisphosphonate drug
zoledronate significantly reduced the recurrence of breast cancer in premenopausal women
with estrogen-receptor-positive breast cancer. Similar results were reported previously
for hormone-refractory prostate cancer. But zoledronate quickly binds to bone, reducing
its efficacy in other tissues.
Energy drinks may be harmful to
people with hypertension, heart disease
People who have high blood pressure or
heart disease should avoid consuming energy drinks, according to a Henry Ford Hospital
study to be published online Wednesday in the Annals of Pharmacotherapy.
Researchers found that healthy adults who drank two cans a day of a popular energy drink
experienced an increase in their blood pressure and heart rate. No significant changes in
EKG measurements were reported.
The increases in blood pressure and heart rate were insignificant for healthy adults, but
could prove harmful to people with a heart-related condition, says James Kalus, Pharm.D.,
senior manager of Patient Care Services at Henry Ford Hospital and lead author of the
study. "Based on our findings, we recommend that people who have hypertension or
heart disease and are taking medication for them to avoid consuming energy drinks because
of a potential risk to their health," Dr. Kalus says. Researchers believe the
caffeine and taurine levels in energy drinks could be responsible for increases in blood
pressure and heart rate. The brand of energy drink used in the study is not being
identified because most energy drinks on the market boast similar levels of caffeine and
taurine, a non-essential amino acid derivative often found in meat and fish. The caffeine
levels in energy drinks are equivalent to at least one to two cups of coffee. Dr. Kalus
says energy drinks should not be confused with sports drinks, which aim to replenish the
carbohydrates and electrolytes that a body needs.
UC San Diego Biologists Discover a
Protein Link to Wound Healing
Diabetes and eczema may appear to be two
completely unrelated diseases. But UC San Diego biologists have uncovered what appears to
be a crucial biochemical link between the two.The scientists report in the March 26 issue
of the journal Nature their discovery that a protein previously linked only to cell death,
plays a critical role in the healing of wounds in laboratory mice. This protein, known as
caspase 8, is deficient in humans with eczema, but produced in excess amounts by
diabetics. The researchers say their discovery may explain why many diabetics lack a
normal wound response and suffer severe complications from minor cuts and scrapes, and why
those with eczema exhibit a chronic inflammation of the skin that compromises its
protective function.
'Master regulator' of skin
formation discovered
Researchers at Oregon State University have
found one gene in the human body that appears to be a master regulator for skin
development, in research that could help address everything from skin diseases such as
eczema or psoriasis to the wrinkling of skin as people age. Inadequate or loss of
expression of this gene, called CTIP2, may play a role in some skin disorders, scientists
believe, and understanding the mechanisms of gene action could provide a solution to them.
"We found that CTIP2 is a transcriptional factor that helps control different levels
of skin development, including the final phase of a protective barrier formation,"
said Arup Indra, an OSU assistant professor of pharmacy. "It also seems particularly
important in lipid biosynthesis, which is relevant not only to certain skin diseases but
also wrinkling and premature skin aging."
The findings of this research, done in collaboration with Mark Leid, OSU professor of
pharmacy, were recently published in the Journal of Investigative Dermatology. This work
is supported by the National Institutes of Health, which has provided $1.5 million for its
continuation. Skin is actually the largest organ in the human body, and has important
functions in protecting people from infection, toxins, microbes and solar radiation. But
it's not static – skin cells are constantly dying and being replaced by new cells, to
the extent that human skin actually renews its surface layers every three to four weeks.
Wrinkles, in fact, are a reflection of slower skin regeneration that occurs naturally with
aging. Major advances have been made in recent years in understanding how skin develops in
space and time, and in recent breakthroughs scientists learned how to re-program adult
skin cells into embryonic stem cells.
Inconsistent performance speed
among children with ADHD may underlie how well they use memory
Children with attention-deficit
hyperactivity disorder (ADHD) show more variable or inconsistent responses during on
‘working’ or short-term memory tasks when compared with typically developing
peers, a study by UC Davis M.I.N.D. Institute Julie Schweitzer has found. “We think
poor working memory is a characteristic present in many children and adults with
ADHD,” said Schweitzer, an associate professor in the Department of Psychiatry and
Behavioral Sciences. “Our study helps explain why working memory may be fine at one
moment and poor at another, just as one day a child with ADHD seems to be able to learn
and focus in class and on another day seems distracted and not paying attention,”
Schweitzer said. According to the national Centers for Disease Control and Prevention
(CDC), an estimated 4.4 million youth, ages 4 to17, have been diagnosed with ADHD by a
healthcare professional. In 2003 nearly 8 percent of school-aged children were reported to
have an ADHD diagnosis by their parent. The current study, published online in February in
the journal Child Neuropsychology, supports the idea that what underlies impaired working
memory is a problem in how consistently a child with ADHD can respond during a working
memory task. “We have known for some time that children with ADHD vary in how fast
they are able to complete working memory tasks when compared to normally developing
control subjects,” Schweitzer explained .
Tell me where you research and
I’ll tell you who you work with
A joint project by the Carlos III
University, the University of Extremadura and the Spanish National Research Council (CSIC)
has analysed researchers’ preferences when it comes to seeking partners to co-author
articles. Catalonia and Cantabria are the two regions with the most active researchers,
while those in the Balearic Islands rely most on international colleagues.Scientists at
Madrid’s Carlos III University, the University of Extremadura and the CSIC’s
Institute of Public Goods and Policies have collaborated to produce a study called An
Examination of scientific university co-authorship in Spain, which has analysed patterns
of inter-university collaboration in the country. The social networks model was used to
carry out the study. The research project, published in the latest issue of the journal
Aslib Proceedings, analyses all the issues relating to the production of scientific work
in Spain – the number of projects conducted without collaboration, the places where
participating researchers tend to come from, and the factors governing the origin of the
researchers chosen. The study’s authors, Carlos Olmeda, Antonio Perianes and Mª
Antonia Ovalle, tell SINC that “we were interested in looking into unknowns such as
the degree of cooperation in co-authorship practices between Spanish university
researchers at national level, to see whether there is a hierarchy in terms of
collaboration between Spanish universities, and to analyse the impact of collaborative
production”.The study’s conclusions show that, in Spain, “six out of every
ten articles are written in collaboration, and three out of every ten with international
partners”.
The egg makes sure that sperm don't
get too old
In contrast to women, men are fertile
throughout life, but research at the Sahlgrenska Academy, University of Gothenburg,
Sweden, has now shown that a fertilising sperm can get help from the egg to rejuvenate.
The result is an important step towards future stem cell therapy. The risk of chromosomal
abnormalities in the foetus is highly correlated to the age of the mother, but is nearly
independent of the age of the father. One possible explanation is that egg cells have a
unique ability to reset the age of a sperm. "We are the first to show that egg cells
have the ability to rejuvenate other cells, and this is an important result for future
stem cell research", says Associate Professor Tomas Simonsson, who leads the research
group at the Sahlgrenska Academy that has made this discovery. Each time a cell divides,
the genetic material at the ends of the chromosomes becomes shorter. The ends of the
chromosomes, known as "telomeres", are important for the genetic stability of
the cell and they act as a DNA clock that measures the age of the cell. The cell stops
dividing and dies when the telomeres become too short. The discovery that the egg cell can
extend the telomeres of a fertilising sperm cell is important in the development of stem
cell therapy. Stem cell therapy involves replacing the cell nucleus in unfertilised egg
with a nucleus from a somatic cell that has come from a patient who needs a stem cell
transplantation. As soon as the cell has divided a few times, it is possible to harvest
stem cells that are then allowed to mature to the cell type that the recipient needs.
Westminster showcase for animal
replacement research
Researchers from The University of
Nottingham will be in Westminster today to talk to MPs about how innovative scientific
advances could reduce the need for animal experimentation in the quest to find new
treatments for the painful degenerative joint condition osteoarthritis. Dr Ali Mobasheri,
Associate Professor and Reader in Comparative Physiology at the University’s School
of Veterinary Medicine and Science, and PhD postgraduate student Abigail Clutterbuck will
showcase their research at a poster event organised by the National Centre for the
Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in the House of
Lords. Their work has been chosen as fine examples of research supporting the ethos of the
centre, which provides a UK focus for the promotion, development and implementation of the
3Rs — replacement, refinement and reduction — in animal research and testing. Dr
Mobasheri and Abigail both conduct research into developing our understanding of
osteoarthritis, a painful and debilitating condition, which is the most common cause of
joint disease in both humans and pets. It is hoped that by finding out more about how the
condition progresses, new treatments and therapies can be developed to help relieve the
symptoms of sufferers, which can include pain, inflammation and loss of mobility.
Daily consumption of cannabis
predisposes to the appearance of psychosis and schizophrenia
The daily consumption of cannabis
predisposes to the appearance of psychosis and schizophrenia, and those episodes of
psychosis which are fruit of this substance present certain specific characteristics, both
before their appearance and in the clinical presentation of the psychosis. This is one of
the conclusions of the doctoral thesis "Neurodevelopment and environmental stress in
initial psychosis: transversal analysis of the ESPIGAS study", carried out by
researcher Miguel Ruiz Veguilla, of the Institute of Neurosciences of the University of
Granada (Spain) and supervised by professors Manuel Gurpegui Fernández de Legaria and
Jorge Cervilla Ballesteros. Ruiz Veguilla is also the person in charge fo the Unit of
Development Neuropsychiatry of Jaén (Spain). This work has studied the risk factors
associated with schizophrenia, identifying and characterizing in depth those psychosis
associated with a continual consumption of cannabis. They carried out a study with 92
subjects, 50 of which had developed a psychosis without presenting signs of an
"abnormal neurodevelopment", this is, they had been doing well academically,
they had a group of friends (no social isolation) and they presented a good motor
coordination. In addition, these subjects did not show a family history of episodes of
psychosis in first or second degree.
Fructose metabolism by the brain
increases food intake and obesity
The journal Biochemical and Biophysical
Research Communications (http://www.elsevier.com/locate/ybbrc) (BBRC), published by
Elsevier, will publish an important review this week online, by M. Daniel Lane and
colleagues at Johns Hopkins, building on the suggested link between the consumption of
fructose and increased food intake, which may contribute to a high incidence of obesity
and Type 2 diabetes. Over the past four decades life-styles have gravitated toward the
excessive consumption of 'high energy' foods and sedentary behavior that has resulted in a
high incidence of obesity and its pathological consequences. This scenario has led to the
increased occurrence of insulin resistance and Type 2 diabetes. At present, approximately
thirty percent of adult Americans can be classified as obese. Moreover, these changes now
extend into the younger age group.M. Daniel Lane and co-workers at The Johns Hopkins
University School of Medicine in Baltimore have now pulled together work, largely in their
laboratory (many papers beginning in 2000), dealing with the role of malonyl-CoA in the
signaling system in the brain (specifically the hypothalamus) that has inputs into the
higher brain centers that determine feeding behavior, most notably appetite. Two papers in
the journal PNAS in 2007 and 2008 showed that glucose and fructose act quite differently
in the brain (hypothalamus) - glucose decreasing food intake and fructose increasing food
intake. Both of these sugars signal in the brain through the malonyl-CoA signaling pathway
and have inverse effects on food intake.Lane commented "We feel that these findings
may have particular relevance to the massive increase in the use of high fructose
sweeteners (both high fructose corn syrup and table sugar) in virtually all sweetened
foods, most notably soft drinks. The per capita consumption of these sweeteners in the USA
is about 145 lbs/year and is probably much higher in teenagers/youth that have a high
level of consumption of soft drinks. There is a large literature now that correlates, but
does not prove that a culprit in the rise of teenage obesity may be fructose."The
fact that fructose metabolism by the brain increases food intake and obesity risk raises
health concerns in view of the large and increasing per capita consumption of high
fructose sweeteners, especially by youth.
Queen's scientists find new way to
battle MRSA
Experts from Queen's University Belfast
have developed new agents to fight MRSA and other hospital-acquired infections that are
resistant to antibiotics. The fluids are a class of ionic liquids that not only kill
colonies of these dangerous microbes, they also prevent their growth. The development of
these new antimicrobial agents was carried out by a team of eight researchers from the
Queen's University Ionic Liquid Laboratories (QUILL) Research Centre. The team was led by
Brendan Gilmore, Lecturer in Pharmaceutics at the School of Pharmacy, and Martyn Earle,
Assistant Director of QUILL. The discovery is published in the scientific journal Green
Chemistry. Many types of bacteria, such as MRSA, exist in colonies that adhere to the
surfaces of materials. The colonies often form coatings, known as biofilms, which protect
them from antiseptics, disinfectants, and antibiotics. Earle said "We have shown that
when pitted against the ionic liquids we developed and tested, biofilms offer little or no
protection to MRSA, or to seven other infectious microorganisms."
Ionic liquids, just like the table salt sprinkled on food, are salts. They consist
entirely of ions - electrically-charged atoms or groups of atoms. Unlike table salt,
however, which has to be heated to over 800o C to become a liquid, the ionic liquid
antibiofilm agents remain liquid at the ambient temperatures found in hospitals. One of
the attractions of ionic liquids is the opportunity to tailor their physical, chemical,
and biological properties by building specific features into the chemical structures of
the positively-charged ions (the cations), and/or the negatively-charged ions (the
anions).Earle said "Our goal is to design ionic liquids with the lowest possible
toxicity to humans while wiping out colonies of bacteria that cause hospital acquired
infections."
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 body's 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. The molecule NF-?B is activated by inflammation,
which plays a key role in autoimmune disease development, making NF-?B a prime candidate
to track autoimmune activity. Researchers at the University of Oslo led by Drs. Ludvig
Munthe and Bjarne Bogen in collaboration with Rune Blomhoff engineered NF-?B such that it
would emit light when activated. Using a mouse model of systemic autoimmunity with
features of lupus, they found that NF-?B activation signals were present in affected
organs several weeks before the clinical manifestations of disease. The light signal
intensity correlated with disease progression. NF-?B tracking may therefore provide a new
tool in the evaluation of early autoimmune therapies.
Discovery may result in new test to
determine predisposition to cancer
Researchers at UCLA's Jonsson Comprehensive
Cancer Center have developed an assay that may be used to help identify new genes that can
predict a predisposition to cancer. The study, published in the April issue of Radiation
Research, was done in yeast and mammalian cells. Cancer cells show persistent genetic
instability and the researchers, led by Robert Schiestl, have discovered a mechanism that
switches on that genetic instability. If they can uncover and understand the molecular
pathways at work in promoting genetic instability, they may be able to develop ways to
switch that mechanism off, restoring stability.
"We all have several hundred cells in our body that go crazy every day, and they're
taken out by our immune system," said Schiestl, a professor of pathology, radiation
oncology and environmental health sciences and a Jonsson Cancer Center scientist.
"What's important is that those cells don't grow and spread and invade other regions
of our body. Cancer cells are able to grow, spread and invade because the continued
genetic instability can disturb the cellular program and create a growth advantage.
Unfortunately, the immune system is not very effective at taking cancer cells out."
The assay determines the efficiency of the repair mechanism when DNA suffers a
double-strand break, when both strands in the double helix are severed. These breaks cause
genetic instability and are particularly dangerous because they can lead to genome
rearrangements or deletions of certain genes that, when gone, result in cancer.
"Every cell has double strand breaks all the time," said Schiestl, senior author
of the study. "It is how the cell tries to fix these breaks that is key, the capacity
and the efficiency of the repair so no further harm occurs."
Imaging technique may trace
development of Parkinson's disease
While finding a biomarker for Parkinson's
disease that would let physicians screen for or track its progression remains an elusive
goal, a team led by a University of Illinois at Chicago neuroscientist has shown that a
non-invasive brain scanning technique offers promise. The tool may also help advance the
development of new drugs or neuroprotective agents to treat or ward off Parkinson's. The
findings, now online, will appear in a forthcoming issue of Neurology. David Vaillancourt,
assistant professor of kinesiology at UIC, along with colleagues from UIC and Rush
University, used a type of MRI scan called diffusion tensor imaging on 28 subjects, half
with early symptoms of Parkinson's and the other half without. They scanned an area of the
brain called the substantia nigra, a cluster of neurons that produce the neurotransmitter
dopamine. Parkinson's patients have been found to have about half the number of
dopaminergic neurons in certain areas of the substantia nigra as those without the
disease. Determining loss of dopaminergic neurons using conventional methods such as
metabolic PET scans is expensive, invasive, and requires injection of radioactive tracer
chemicals. But the method studied by Vaillancourt and his group is non-invasive,
relatively inexpensive, and does not use radioactive tracers. "We're suggesting it's
possible to eventually diagnose Parkinson's disease non-invasively and objectively by
examining the part of the brain thought to underlie the causes of the disease," said
Vaillancourt. No tool currently available can do that, he said.
Experimental Parkinson's therapy
may have robust weight-loss effect
A growth factor used in clinical
experiments to rescue dying brain cells in Parkinson patients may cause unwanted weight
loss if delivered to specific areas of the brain, according to University of Florida
researchers in the March online edition of Molecular Therapy. The discovery is a
cautionary warning for experimental treatments to treat Parkinson's disease that use GDNF,
short for glial cell line-derived neurotrophic factor. In addition, the finding broadens
understanding of the brain's role in the regulation of metabolism and body weight,
suggesting that gene therapy techniques in the brain potentially could control obesity.
"People shouldn't interpret our result to mean this is a terrible side effect that
precludes ability to do GDNF gene therapy for Parkinson's disease, but it does show that
it is extremely important to place the therapy in the correct brain region," said Ron
Mandel, a professor of neuroscience at UF's McKnight Brain Institute and the Powell Gene
Therapy Center. "The good news for Parkinson's patients is that the finding doesn't
discredit the current target." Parkinson's disease affects between 500,000 and 1.5
million Americans, causing patients to gradually develop movement problems, including
tremors, stiffness and slowness of movement. Current treatments only address symptoms and
do nothing to slow the disease's progression, which is caused by degeneration and death of
nerve cells that produce dopamine, a substance necessary for communication between cells
that coordinate movement. GDNF rescues the dopamine-producing cells in cell cultures and
animal models of Parkinson's disease. But Parkinson patients were disappointed in
September 2004 when the biotechnology company Amgen discontinued a clinical trial using
GDNF because of concerns about safety and effectiveness. The therapy was delivered through
surgically implanted catheters to a region called the putamen, and several patients said
their physical conditions and quality of life improved. A different approach in a more
recent trial by the biopharmaceutical company Ceregene involved gene therapy, in which the
gene to produce neurturin, a sister protein to GDNF, was transferred into the putamen
region of Parkinson patients. But it showed no marked effectiveness.
