US Govt awards $170 million to fund stem cell research

The US National Heart, Lung, and Blood Institute (NHLBI), one of the US National Institutes of Health, has awarded US$170 million to be paid over seven years to 18 teams of research scientists to develop the high-potential field of stem and progenitor cell tools and therapies.

The awards create the NHLBI Progenitor Cell Biology Consortium, which will bring together researchers from the heart, lung, blood, and technology research fields. A sevenyear project, the consortium assembles nine research hubs with multidisciplinary teams of principal investigators and an administrative coordinating centre to focus on progenitor cell biology.

While a stem cell can renew itself indefinitely or differentiate, a progenitor cell can only divide a limited number of times and is often more limited than a stem cell in the kinds of cells it can become. Given the potential of these cells for clinical applications, the goals of the consortium are to identify and characterise progenitor cell lines, direct the differentiation of stem and progenitor cells to desired cell fates, and develop new clinical strategies to address the unique challenges presented by the transplantation of these cells.

“NHLBI is committed to stimulating stem cell research that will lead to the development of regenerative therapies for the treatment of heart, lung, and blood diseases,” said NHLBI Director Elizabeth G. Nabel, MD. “Important gaps remain in our understanding of stem and progenitor cells, and this consortium holds great promise to expand our knowledge and uncover therapeutic applications of great public impact.”



Comprehensive CT scan gives better indication of CAD

A team of researchers led by Massachusetts General Hospital (MGH) radiologists has developed a computedtomography- based protocol that identifies both narrowing of coronary arteries and areas of myocardial ischemia, giving a better indication of clinically significant coronary artery disease. Their report appears in the 15 September issue of the Journal of the American College of Cardiology.

“This is among the first demonstrations of the use of cardiac CT to detect both coronary artery stenosis and resulting myocardial ischemia simultaneously in a single examination,” said Ricardo C. Cury, MD, a cardiac imaging specialist at the MGH Heart Center and the study’s principal investigator.

CT can detect plaques in coronary arteries, but their appearance may not indicate whether or not they actually compromise the heart muscle’s blood supply. More detailed angiographic images obtained via invasive cardiac catheterization give a better picture of how obstructive a plaque may be, and perfusion studies utilising technologies such as MRI scans or the nuclear medicine technologies SPECT and PET reveal areas where limited blood flow has damaged the heart muscle, information that can determine whether a patient can be treated with drugs or requires surgical intervention.

The MGH-led study was designed to see whether a comprehensive cardiac CT examination could incorporate myocardial perfusion studies in both resting and stress situations along with the anatomic data provided by CT angiography. The study enrolled 34 cardiac patients who recently had SPECT stress tests and were likely to also require angiography via cardiac catheterization.

Participants first had a cardiac CT taken while receiving an infusion of adenosine, which produces physiologic stress symptoms such as elevated heart rate and blood pressure. When vital signs returned to normal several minutes after the adenosine infusion, a resting cardiac CT was taken. Both of those scans involved the use of contrast material, and to detect areas with little or no contrast agent – indicating restrictions to the myocardial vasculature – a third CT scan was taken 7 minutes later.

The accuracy of CT-based perfusion imaging in diagnosing coronary artery narrowing that significantly affected myocardial perfusion was virtually the same as SPECT stress imaging, and the results of coronary CT angiography also compared favorably to those of cardiac catheterization. Because the investigators used new radiation-dose-reduction techniques, the radiation dose of the three CT scans did not exceed the dosage involved in the SPECT stress perfusion study.

“The ability to acquire anatomical visualisation of coronary artery stenosis together with physiological assessment of myocardial perfusion in a single study could improve diagnostic accuracy while potentially reducing costs and radiation exposure. Since our study was relatively small, we need to test this approach in a larger multicenter trial and further investigate the additional value of CT perfusion studies over CT angiography,” Dr Cury said.



Bell’s Palsy: Study calls for rethink of cause and treatment

Drugs widely prescribed to treat facial paralysis in Bell’s palsy are ineffective and are based on false notions of the cause of the condition, according to Cochrane Researchers. They say research must now focus on discovering other potential causes and treatments.

Between 11 and 40 people in every 100,000 are affected by the condition, which causes paralysis on one side of the face. Paralysis is usually temporary, but a third of people suffer ongoing problems including facial disfigurement, pain and psychological difficulties.

Antiviral medications are widely prescribed to treat the condition, because studies have indicated that Bell’s palsy may be associated with the same virus that causes cold sores (herpes simplex). Previous Cochrane Systematic Reviews did not find sufficient evidence to determine whether or not antiviral medications are effective.

In the current review, the researchers considered data from seven trials that together include 1,987 people. Antivirals were no more effective than placebo. Antivirals were also significantly less effective than steroid drugs called corticosteroids which will be the subject of another Cochrane Review in progress.

“The evidence from this review shows that antivirals used for herpes simplex offer no benefit for people with Bell’s palsy. These results cast doubt on research that suggests herpes simplex causes the condition,” said Pauline Lockhart, who is based at the Centre for Primary Care and Population Research at the University of Dundee. “In view of this, further research should be aimed at discovering alternative causes and treatments.”

● Citation: Lockhart P et al. Antiviral treatment for Bell’s palsy (idiopathic facial paralysis). Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD001869. DOI: 10.1002/14651858.CD001869. pub4.

● The Cochrane Library contains high quality health care information, including Systematic Reviews from The Cochrane Collaboration. These Reviews bring together research on the effects of health care and are considered the gold standard for determining the relative effectiveness of different interventions. The Cochrane Collaboration is a UK registered international charity and the world's leading producer of systematic reviews. Visit: www.thecochranelibrary.com



Viral association with chronic fatigue syndrome

Scientists have discovered a potential retroviral link to chronic fatigue syndrome, known as CFS, a debilitating disease that affects millions of people worldwide. Researchers from the US-based Whittemore Peterson Institute (WPI), at the University of Nevada, Reno, the US National Cancer Institute (NCI), and the Cleveland Clinic, report this finding online 8 October 2009, issue of Science.

“We now have evidence that a retrovirus named XMRV is frequently present in the blood of patients with CFS. This discovery could be a major step in the discovery of vital treatment options for millions of patients,” said Judy Mikovits, PhD, director of research for WPI and leader of the team that discovered this association. Researchers cautioned however, that this finding shows there is an association between XMRV and CFS but does not prove that XMRV causes CFS.



Gears of the mammalian circadian clock exposed

The circadian clock, a 24-hour metabolic rhythm governing sleep cycles and other physiological processes, has long been known to play a central role in regulating the daily activities of living organisms. Its detailed biochemical mechanisms, however, have largely remained a mystery.

That mystery is one step closer to being unravelled with the latest discovery by a research team led by Hiroki R. Ueda of the RIKEN Center for Developmental Biology and Joseph S. Takahashi of Northwestern University, published in the Proceedings of the National Academy of Sciences.

Researchers analysed 1,260 pharmacologically active compounds in mouse and human clock cell lines and identified 10 which exerted the greatest impact on the clock cycle. Surprisingly, all but one were found to target a single enzyme (casein kinase I ε/δ), the inhibition of which, researchers showed, dramatically extends this cycle from 24 hours to more than 48 hours.

The possibility that the circadian clock may be regulated by relatively simple processes involving only a handful of molecules, as indicated by this result, overturns conventional thinking on the topic. The more important finding that the inhibition process identified is insensitive to changes of as much as 10 degrees Celsius further hints at a breakthrough in the related puzzle of temperature compensation: how circadian clocks maintain constant periodicity over a broad range of temperatures.

Taken together, these findings suggest the need to fundamentally revise existing models of the mammalian circadian clock. They also point the way toward novel approaches to treatment of sleeping disorders and other debilitating clock-related conditions.



Exercise recommended for rheumatoid arthritis

Exercise programmes designed to improve strength and stamina are safe and effective treatments for rheumatoid arthritis (RA), according to a new Cochrane Systematic Review. The researchers reviewed dynamic exercise programme trials in RA patients and found moderate benefits associated with this type of treatment.

“Based on the evidence in this study, we would recommend aerobic capacity training combined with muscle strength training as routine practice for RA patients,” said lead researcher Emalie Hurkmans of the Leiden University Medical Center in Leiden, Netherlands. “But we need more research to establish the recommended length and type of exercise programmes, whether patients need to be supervised and if these programmes are cost effective.”

RA affects up to 1 in 100 people in Western countries, causing chronic pain and inflammation of the joints. There is currently no cure for the disease, so dynamic exercise programmes are often recommended as a complement to drug therapy to try to improve physical function through physical exercise.

The researchers combined data from eight trials involving a total of 575 patients. The results reaffirm the previous study’s findings that dynamic exercise programmes are safe and have positive effects on aerobic capacity and muscle strength in RA patients, and when performed long term also have a positive effect on functional ability. However, the researchers say the benefits are only seen immediately after the intervention. They also suggest water-based programmes may help to improve functional ability of patients.

“One important omission from this study is evidence for long term follow-up effects, so without further studies we can’t rule out that the obtained effects vanish if exercise programmes are not continued over long periods. There are also other types of exercise that weren’t included in our review, such as flexibility and stability training, and it would be interesting to find out whether these also have positive effects,” said Hurkmans.

● Citation: Hurkmans E et al. Dynamic exercise programs (aerobic capacity and/or muscle strength training) in patients with rheumatoid arthritis. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD006853. DOI: 10.1002/ 14651858.CD006853.pub2.



Rapid viral diagnosis tests in emergency rooms

Rapid viral diagnosis tests for respiratory diseases in children who arrive in emergency departments have the potential to reduce pressures on health systems by enabling doctors to reach a quicker diagnosis, according to Cochrane Researchers. However, they say larger trials are needed to confirm this finding.

“The existing evidence is not strong enough to prove that these tests help to reduce pressure on health systems, but it certainly does look promising,” said lead researcher, Quynh Doan of the British Columbia Children’s Hospital in Vancouver, Canada.

Children who are admitted to emergency departments with cold and flu symptoms and fever undergo various diagnostic tests and are often prescribed antibiotics as a precautionary measure, even though viruses, which are often the cause, do not respond to antibiotics. The burden on health systems is huge, not only financially, but also in terms of the time and staff required to reach a diagnosis. Rapid viral diagnosis methods could help deliver fast, accurate diagnoses, and enable a much more appropriate use of antibiotics.

The study included data from four trials, which together included 1,588 children. There was some evidence that rapid viral testing reduced use of other blood or urine tests, chest X-rays and antibiotics, but the results were not significant. However, the researchers suggest that further, sufficiently large studies could reveal the true impact of faster tests.

“A large controlled trial would help us to understand whether rapid viral testing can be of any great benefit,” says Doan. “For example, we saw a weak trend towards reduced antibiotic prescriptions, but results were contradictory between the different trials. It would also be interesting to see some evaluation of cost effectiveness for these more rapid tests.”

● Citation: Doan Q, et al. Rapid viral diagnosis for acute febrile respiratory illness in children in the Emergency Department. Cochrane Database of Systematic Reviews 2009, Issue 4.Art.No.: CD006452. DOI: 10.1002/ 14651858.CD006452.pub2.



Methotrexate shown to work against hereditary cancers

Cancer research scientists in the United Kingdom have shown that an early chemotherapy drug invented in the 1940s has the potential to work against a genetic fault called HNPCC (hereditary non-polyposis colorectal cancer) which is linked to bowel and other cancers. The results are published in the 27 August issue of EMBO Molecular Medicine.

HNPCC is a hereditary condition involved in around 5% of all bowel cancer cases. As well as bowel cancer, it puts people at increased risk of developing stomach, womb, ovarian, kidney and other cancers. Almost 40% of people with HNPCC have a faulty MSH2 gene.

Scientists at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) in London sought to improve treatments for people with cancer caused by HNPCC by finding drugs which selectively kill cells containing the damaged MSH2 gene. In this study, they tested a range of drugs on cells with the faulty MSH2 gene and found that the drug methotrexate worked particularly well in destroying these cells.

This study suggests that methotrexate could help to treat people whose cancer is driven by the MSH2 genetic fault, potentially opening the door to a more targeted treatment option. A new clinical trial has begun at The Royal Marsden NHS Foundation Trust to see how well methotrexate treats patients with advanced bowel cancer.

Methotrexate is similar to a normal molecule called folinic acid, which is required for copying DNA. The drug prevents cells from making and repairing DNA – a process needed for cancer growth. It was one of the first chemotherapy drugs to be invented in the 1940s and is still used to treat a number of cancer. But until now, it has not commonly been used to treat people with HNPCC.



Researchers to develop low cost system to decode genome

In an effort to build a nanoscale DNA sequencer, IBM scientists are drilling nano-sized holes in computerlike chips and passing DNA strands through them in order to read the information contained within their genetic code.

This research to demonstrate a silicon-based “DNA Transistor” could help pave the way to read human DNA easily and quickly, generating advances in diagnosis and treatment. The challenge is to slow and control the motion of the DNA through the hole so the reader can accurately decode the DNA. If successful, the project could improve throughput and reduce the cost of a personalised genome analysis to less than a US$1,000. In comparison, the first sequencing ever done by the Human Genome Project (HGP) cost $3 billion.

A team of IBM scientists from four fields – nanofabrication, microelectronics, physics and biology – are converging to master the technique that threads a long DNA molecule through a three nanometer wide hole, known as a nanopore, in a silicon chip. As the molecule is passed through the nanopore, it is ratcheted one unit of DNA at a time, as an electrical sensor “reads” the DNA.

“The technologies that make reading DNA fast, cheap and widely available have the potential to revolutionise biomedical research and herald an era of personalised medicine,” said IBM research scientist Gustavo Stolovitzky. “Ultimately, it could improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine and those who are most at risk of adverse reaction.”

Slowing the speed is critical to being able to read the DNA strand. IBM scientists believe they have a unique approach that could tackle this challenge.



WCMC-Q students in breakthrough sleep study

Cornell psychology professor and best selling author James Maas, PhD, is including WCMC-Q premedical students in his latest study on the relationship between sleep and overall health.

“This is a huge study and it’s got a nice cross-cultural element,” said Dr Maas, who was in Doha mid October to give lectures to WCMC-Q students for his Psychology 101 course. “I’m excited to conduct this study in Qatar as well as in New York because I think students in Doha could benefit from giving sleep more of a priority. Many students in Doha practice a very nice custom of spending time with their parents and grandparents, but it’s a custom that could take away from study time and sleep time. We’re seeing a lot of students trying to survive on five or six hours when they are supposed to have at least nine.”

“Sleep deprivation affects alertness and it shortens your life,” continued Dr Maas, whose book Power Sleep topped the best-selling book charts in the US when it was released.

At Cornell University in Ithaca, New York, Dr Maas’ Psychology 101 course draws as many as 1300 students, making it the largest live lecture in the US. While working on his latest book, which reviews sleep-monitoring systems, he is studying 450 of his students from Ithaca and Qatar. He considers the study especially pertinent to medical students.

“More than a few doctors aren’t getting enough sleep, and this affects everything, including their energy level, stamina, how patient they are with their patients, how quickly they can diagnose uncommon disorders and how quickly they can pick up and parse out treatments,” Dr Maas said. In addition, he says there are at least 89 definable sleep disorders.

To collect data for the study, students used Zeo for several nights. Zeo consists of a wireless headband that monitors brainwaves and a small alarm clock-like bedside display. The bedside display receives signals from the headband, interprets which phase of sleep you are in, and displays your sleep data. Each morning, the students received a sleep score, called ZQ, and, over the course of the study, analysed their own their sleep trends to apply what they learned in the classroom.



New insight in fight against Leishmania parasite

Professor Albert Descoteaux’s team at Centre INRS – Institut Armand-Frappier in Canada, has gained a better understanding of how the Leishmania donovani parasite manages to outsmart the human immune system and proliferate with impunity, causing visceral leishmaniasis, a chronic infection that is potentially fatal if left untreated. This scientific breakthrough was recently published 16 October 2009 in PLoS Pathogens.

Some 350 million people live in areas where leishmaniasis can be contracted. Over 90% of cases are reported in India, Bangladesh, Nepal, Sudan, and Brazil. Leishmaniasis is also found Iraq. There are no effective vaccines to prevent leishmaniasis and resistance issues greatly reduce the efficacy of conventional medications.

The parasite, which is transmitted to humans during the blood meal of infected sand flies, is internalised via macrophages in the liver, spleen, and bone marrow. However, this parasite manages to alter the normal phagocytosis process (destruction of foreign bodies), resist this process, replicate itself, and infect other macrophages. This resistance process notably involves blocking the normal acidification process within the macrophage by disrupting membrane fusions.

To date, few studies have attempted to identify the regulators of these membrane fusions and their role in the phagolysosomal biogenesis process (a compartment where pathogenic microorganisms are usually killed). The work by doctoral candidate Adrien Vinet and Professor Descoteaux shed new light on the biology of Leishmania parasites, particularly the molecular mechanisms by which they manage to outsmart the human immune system.

                                  
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