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windfall. white arrows indicate weaknesses in the blood vessels of mice with HHT ( environment) than healthy mice ( left ) did not. Thalidomide strengthens the vessel walls ( right ).
Lebrin et al, Nature Medicine, Advance Online Publication (2010)
Despite its horrific history of causing birth defects, thalidomide has recently made a comeback as a treatment for diseases such as multiple myeloma cancer. Now, a new study suggests that the drug may also relieve symptoms of a genetic disease called hereditary hemorrhagic telangiectasia, a discovery that could help researchers to new therapies for VRL and other vascular diseases.
In the late 1950s and early 1960s, doctors prescribed thalidomide as an anti-nausea drug for pregnant women with a regularity that proved tragic. More than 10,000 children in 46 countries were born with missing limbs and other defects before thalidomide manufacturers have pulled from the market. Researchers have recently begun to understand how the drug made its damage. They know little about one of the benefits of the drug Thalidomide appears to control angiogenesis, the growth of new blood vessels. This property makes it a powerful weapon against some cancers, but scientists do not know how it works.
In HHT, blood vessels grow without the right support cells to maintain stable and solid. Patients have leaking vessels and are subject to potentially fatal bleeding in the brain, lungs, liver and gastrointestinal tract. People with the rare hereditary disease also have frequent nosebleeds, as much as seven a day, which can become so severe that patients require skin grafts in their nose or even more desperate measures to lead a normal life. "Patients VRL get their nostrils sewn just so they can walk down the street," says Christine Mummery, a developmental biologist at the Medical Center of the University of Leiden in the Netherlands.
The addiction thalidomide for targeting blood vessels in tumors is Mummery ask whether the drug's effect on angiogenesis could help people with HHT. When they gave thalidomide seven HHT patients, six had significantly fewer nosebleeds in the month of their first dose, Mummery and his colleagues report online today in Nature Medicine .
to find the mechanism underlying the improvement of patients, researchers tested the drug on mice high to have HHT symptoms. They found that although high doses of thalidomide stop angiogenesis, lower doses actually strengthen blood vessels by stimulating cell growth. Thalidomide seems to pair with a growth factor called PDGF-B to produce more smooth muscle cells that repair defects walled container.
The evidence suggests that the drug works the same way in humans. A nasal biopsy seventh participant (which also saw an improvement, but had to abandon the study because of nerve damage caused by thalidomide) showed layers of smooth muscle cells more than were present in samples from untreated HHT patients. The findings offer new insight about how thalidomide which affects the blood vessels, says Mummery.
They also offer people with HHT hope for more effective therapies in the future, said Paul Oh, an experimental geneticist at the University of Florida, Gainesville, who was not involved in the study. "It is possible thalidomide help with all aspects of HHT," he said. "This is the first major treatment of HHT community works."
The study could well point the way to a more alternative safe, says Rosemary Akhurst, a molecular biologist at the University of California, San Francisco. "ultimately, we do not want anyone to be using a dangerous drug thalidomide," she said. "This can we help take the positive aspects and leave the negative. "
The line most widely used human embryonic stem cells can again be studied with federal dollars. Yesterday, the National Institutes of Health (NIH) has approved four stem cell lines submitted by WiCell, the nonprofit associated with the University of Wisconsin, Madison. The lines include H9, which has been used in more than 500 published studies.
These four lines have been approved under the policy on stem cells in the Bush era, but they had to undergo further monitoring to ensure they meet the rigid rules of ethics issued the last summer the Obama administration. WiCell did not submit requests for lines until two weeks ago. Meanwhile, researchers using H9 worried they might have to cancel research projects. (Researchers had already grants may continue to use the lines of the Bush era, but new grants based on them were waiting.)
The hold-up is because the four lines obtained from embryos that were given to Israel. Collection of documents there and Hebrew translation into English took time, WiCell said in a press release. NIH also added nine lines to the register yesterday by The Washington Post , bringing the total to 64.
A week after J. Craig Venter announced the successful synthesis of a genome and use it to control a cell self- replication, it was on the microphone again, this time to appear before the Committee of the US House energy and commerce. With two other experts in synthetic biology, a bioethicist and Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, Venter sailed a generally favorable round to questions about the benefits and potential risks of synthetic biology. And Fauci said the government is moving quickly to bring synthetic biology to the study of two existing panels that have done a good job of monitoring advanced research in the past.
Fauci stressed the historical record. Decades of work on the genetic code and methods of manipulation, he said, allowed Venter and his colleagues at the J. Craig Venter Institute in Rockville, Maryland, and San Diego, California, to create a genome from scratch and use it to transform a bacterial cell. In the 1970s, caused by the invention of recombinant DNA technology, the scientific community has taken steps to police. Consequently, the National Institutes of Health (NIH) established the Advisory Committee of the recombinant DNA, which oversees genetic engineering. And in the middle of the 1980s, the US government decided the products of genetic engineering could be handled without additional regulator. In 03, in response to concerns about biological research that could be used for civilian or military purposes, NIH established the National Science Advisory Board for Biosecurity face dual use such technology.
Although both councils have no authority on synthetic biology, soon they will be, Fauci told the committee. NIH is reviewing the public comments collected last fall on guidelines for synthetic biology. It provides that the new rules are in June. These rules will include a voluntary program for companies that make the DNA to analyze the controls for all the sequences that could belong to smallpox or other selective agents that could be used for bioterrorism. He did not think additional regulations would be more effective to discourage activities "harmful".
"The guidelines come a big step" to encourage responsible behavior in synthetic biology, Venter said. He also stressed that researchers have been putting genes in and out of organizations without security problems for almost 40 years and that he and others are able to build new organisms that can not survive outside a special environment and therefore would not be a natural threat.
Gregory Kaebnick, a bioethicist at the Hastings Center in Washington, DC, also testified. It is halfway through a 2-year project looking at the ethical implications of synthetic biology. He called for further analysis of whether current and future regulations would be sufficient. "We must guard against overconfidence that we understand the risks," he told the committee.
Written testimony accepted in the back of a coalition of three groups of supervision was even more cautious. ETC Group, the International Center for Technology Assessment, and Friends of the Earth has asked Congress to ban the release of synthetic organisms into the environment and their use in commercial environments. "The time has come for governments to regulate fully all biology and synthetic products," they wrote.
Fixed :. Venter did not draw a self-replicating synthetic cell as this article has already said, but a synthetic genome that was used to control a self-replicating cell
SAN FRANCISCO, California- Clinical peddling unproven treatments stem cells are on the warnings of the International Society for research on stem cells (ISSCR). The company has talked for years against the purveyors of dubious therapies that have a scientific basis with little or no. Now they go a little further. This month, the company launched a new website for patients considering such treatments, which clinics around the world claim can treat tens of lupus paralysis conditions. Clinics that do not meet the minimum standards for independent monitoring of patient safety will soon appear on a blacklist, warning potential patients away.
At the annual meeting of the company here last week, President ISSCR Irving Weissman, a researcher on stem cells at Stanford University, said such clinics prey on vulnerable, often terminally ill patients, taking their money and precious time to their family and loved ones. "And they use us," he told the meeting delegates, when they try to enjoy the legitimate excitement surrounding research on stem cells. He also issued a warning to members of the society: "Some in this audience," he said, lent their names as scientific advisors to some of the clinics in question. Later, at a press conference, he told reporters that the company has sent letters to several members, warning them to dissociate clinics. Those who do not comply will face sanctions or possible expulsion from society, he said.
The website, entitled "Focus on the stem cell treatments," has a comprehensive list of questions for patients and their caregivers to ask about potential treatments and a copy of the Patient Handbook society on stem cell therapies in English, French, German and Italian. It also lists the Top 10 things to know about stem cell treatments, including why and how unproven treatments may be worse than no treatment at all. patients are encouraged to submit the names of clinics, individuals or organizations that provide treatment for the company's experts to review. ISSCR ask the supplier if its treatments have been approved by an independent ethics committee review and if it has the approval of the relevant legal authority, such as the US Food and drug Administration or the European medicines Agency. the clinics that provide sufficient documentation in a few months will be on a list indicating they have appropriate oversight and protection of patients in place. Those who do not appear on a second list of clinics that have failed the exam. The company has received dozens of requests within 2 weeks since the website launched, Weissman said. The examinations will be at least several months, he said, so that the first lists of clinics should appear this fall.
Scientists have been working for decades to develop a vaccine against malaria but the Plasmodium parasite is a formidable enemy. Although a promising vaccine finally reached clinical trials terminal, it provides only partial protection against the disease, which kills up to one million people per year. Now a team of scientists came to what might be relatively simple alternative: two antibiotics widely used already can act as a kind of vaccine against malaria in mice. If the discovery holds in humans, it could be a low-cost and relatively safe tool to help control the disease, they say.
people living in areas where malaria is common to develop a natural immunity, and many scientists have tried to mimic this effect by creating a vaccine using whole parasites, or damaged or killed. Although small human trials have shown good results, production and delivery of such a vaccine will not be cheap. Steffen Borrmann from the School of the University of Heidelberg Medical in Germany and the Kenya Medical Research Institute in Kilifi and his colleagues wondered whether the administration of certain antimalarial drugs to people at high risk of infection could a similar effect.
Drugs scientists had studied are antibiotics that attack a subunit of the malaria parasite called apicoplast, which has some similarities with bacteria. Previous studies had shown that apicoplast-targeting drugs have a delayed death effect: They enable the parasite to grow and replicate in the liver, where the immune system can develop antibodies against invaders. But they block the multiplication of the parasite in the bloodstream, which is where Plasmodium causes symptoms of malaria, including anemia, high fever, and convulsions. The researchers wondered if the treatment of the aggressive malaria with such drugs could be a safe way to allow people to develop a natural immunity. (The drugs are not yet widely used against malaria.)
The researchers tested two of these antibiotics clindamycin and azithromycin, which are used against a range of bacterial infections, a model mouse malaria. They gave the mice a dose of one of the drugs at the same time as they are inoculated with malaria parasites. Parasites infected livers of animals, but none of the mice developed symptoms of malaria. A month later, after all traces of the drug have disappeared from the flow of blood of animals, the animals were still free from the disease: They showed no symptoms after receiving a dose of parasites gave control animals cerebral malaria the most deadly form of the disease. As controls, mice that received only the drug but not parasites in the original protocol also got sick of the challenge dose of Plasmodium , the team announced today online science Translational Medicine .
Azithromycin has a particularly secure balance in infants and pregnant women, the two most vulnerable groups, Borrmann note. He said the combination of azithromycin and chloroquine (a drug against the common malaria), currently approved to treat pregnant women in areas at high risk of malaria would be easy enough to test in an initial human trial. The idea will not work in all areas prone to malaria, he warns. A fairly heavy dose of parasites seems to be necessary to ask a strong immunity, so he said the areas where malaria hits hard during one season would be the best places to try the approach. People could receive a drug dose at the start of the rainy season, which would not prevent infection, but prevent them from developing malaria symptoms. Asymptomatic infection and allow them to develop immunity to the rest of the malaria season. Although the general treatment still carries a risk of emerging resistance to drugs, Borrmann said azithromycin was used in mass campaigns against trachoma without losing its power.
The studies support the idea of using natural exposure in combination with drugs against malaria fighting to help people build up protection against the disease, said the vaccine against malaria researcher Robert Sauerwein medical Center Radboud University Nijmegen in the Netherlands. "It leaves the natural route of infection intact, and may also neutralize the immune evasion strategies used by the parasite."
The H1N1 pandemic that began in the spring of 09 is now officially over, says the World health Organization (WHO). Speaking of Hong Kong on a conference call this afternoon, WHO Director Margaret Chan said "we are now entering the post-pandemic period. The new H1N1 virus has largely run its course. "
The decision reflects the unanimous recommendation of the appointed WHO Emergency Committee, which based its conclusion on recent epidemiological and virological information, especially the southern hemisphere, where flu season is in full swing.
Although the new H1N1 virus is still there and will continue to cause illness, it has become much like any other strain flu, Chan said, not causing most cases of flu, or the outbreak of epidemics during the summer. most experts predict the virus will continue to circulate as an annual strain, and another influenza a strain called H3N2 and influenza B.
on the recommendation of the emergency Committee, WHO officially declared the pandemic 11 June 09, some 3 months after it is believed to have the virus claimed its first victims in Mexico. Since then, there have been some 18,500 laboratory confirmed deaths from the virus, flu expert Keiji Fukuda of the WHO told reporters today in Geneva. The actual toll is believed to be higher; Studies are underway to estimate the total number of excess deaths caused by the virus.
Chan again defended the decision of his agency against accusations that WHO had overreacted and publicized the threat. WHO has always stressed that the pandemic was of "moderate severity," she said, while warning that the virus caused a particularly serious disease in some pregnant women and young adults.
Asked about his feelings now that the episode is over, Chan said: "Do I feel happy that I feel tired, I feel at the time?". She warned that countries must remain vigilant, however, and monitor any unusual behavior by the virus.
The WHO has also been criticized for keeping secret the names of its Emergency Committee, a measure to shield those experts of the excessive pressure. Chan said the names will be published today, but so far they have not appeared on the WHO H1N1 website
The cells of blood coagulation called platelets are generally good, stanching wounds so that we not bleed to death. But for people with lupus, the cells are wicked that aggravate the disease, according to a new study. The work also suggests that a commonly prescribed anticoagulant medication for patients with heart disease could ease the symptoms of lupus.
In lupus, the immune system produces antibodies that target the patient's own cells, which causes joint pain, skin lesions, fatigue, and other symptoms. The blood of lupus is often prone to clotting, and they are more susceptible to heart attack and stroke. These symptoms indicate that platelets play a role in the disease.
immunologist Patrick Blanco of the University of Bordeaux in France and his colleagues wondered if another link platelet could come from a rare breed of warrior immune system known as dendritic cell plasmacytoid name (pDCs). In the bloodstream, pDCs release chemical messengers called type I interferons that rev up the immune system. the lupus patients are too interferon type I, which stimulates the production of auto-antibodies attack causing symptoms. Platelets, in turn, the production of a protein called CD154 that turns on pDCs, and so they could indirectly increase interferon type I output.
To determine if platelets exacerbate lupus pDCs by triggering the immune system to overactivate, Blanco and colleagues from healthy people with blood platelets of patients with lupus mixed. Small balls of antibodies present in the blood of lupus glommed on platelets and on. Activated platelets are CD154, the researchers found, and turn on pDCs, causing them to pump four times the normal amount of a type I interferon In a lupus patient, which could cause the immune system to ramp up his attacks on the body's cells. The team reports its findings online today in Science Translational Medicine .
If switched on platelets worsen lupus, closed cells could alleviate the symptoms of the disease. Thus, researchers dosed mice with lupus imitating clopidogrel (Plavix), a drug that counteracts clotting by preventing platelet activation. In a strain of mice, the clopidogrel curbed the amount of damage to the kidneys, a common consequence and sometimes fatal disease. The compound has also boosted the survival in this strain and another variety of mouse lupus imitating. Blanco said that the platelets are doubly destructive in lupus, the rise of autoimmune attacks and produce potentially fatal clots. So, clopidogrel could be doubly beneficial, he said. His group plans to launch a drug test, which was approved for use in people for more than a decade, patients with lupus.
Mary Crow, an immunologist and rheumatologist at the Hospital for Special Surgery in New York accepts the results. "I think all that platelets play a role" in promoting lupus symptoms, she said. But the work does not convince rheumatologist Lars R ö nnblom of Uppsala University Sweden. He notes, for example, that clopidogrel helped a type of lupus mice mimicking even if the animals are not high levels of type I interferons This suggests that platelets do not necessarily have worse by lupus pDCs prodding, he says, but it does not exempt.
Four scientists have won a Lasker prize for work that includes the discovery of a hormone appetite mediation and discover a protein that stimulates the growth of blood vessels. The Laskers are generally considered the most prestigious award in the US for biomedical research.
Douglas Coleman, who retired from the Jackson Laboratory in Bar Harbor, Maine, after a career studying diabetes and obesity, and Jeffrey Friedman, an obesity researcher at the University Rockefeller in New York, will share the Albert Lasker award for basic medical research for their discovery of the hormone leptin. Fat cells release leptin in the blood and helps control appetite.
An intriguing discovery Coleman described in the late 1960s opened the way for the discovery: It was found that the blood flows sewing together of two mice, one with a disease like diabetes and healthy, caused the healthy animal to begin to reject food. Coleman was assumed that the mouse diabeticlike had released a substance into healthy animals which dampened his appetite. Nearly 30 years later, Friedman identified the protein responsible for what he called leptin after the Greek word "leptos" to "thin." Since the late 190s, there was a huge interest in the operation of leptin as a weight loss drug, but so far, it is proven effective for a small number of people who have a mutation in the receiver of the leptin gene. Yet the discovery of leptin has led to an explosion of interest and new knowledge in appetite and obesity in which the hormone has a central role. "I would not dream leptin so important," said Coleman in an interview.
Clinically, Napoleone Ferrara of Genentech (now owned by the pharmaceutical company Roche), South San Francisco, California, won the award for clinical medical research Lasker ~ DeBakey for 25 years work on angiogenesis, the process by which the body develops new blood vessels. He began the research while a postdoc at the University of California, San Francisco; in 1989, shortly after moving Genentech, he discovers the vascular endothelial growth factor (VEGF), a protein essential for the growth of blood vessels. "I'm actually committed to do something different," said Ferrara in an interview, but it "had discretion" to continue its work on the side of angiogenesis. Ferrara and his colleagues in academia and Genentech then developed a drug that treats macular degeneration by inhibiting VEGF and prevention of abnormal blood vessels form in the retina. This treatment, ranibizumab (trade name Lucentis) was approved by the US Food and Drug Administration in 06. Genentech has also developed a closely related drug, bevacizumab (Avastin brand name) that fight against cancer stifling tumor blood supply. "I feel very fortunate to have been able to follow this story all the way from the beginning," said Ferrara.
The Lasker ~ Koshland Special Achievement Award in Medical Science went to David Weatherall of Oxford University in the UK for decades of work, from the 1950s on thalassemia hereditary disease blood.
Each prize comes with $ 250,000, and winners will be honored at a ceremony next Friday. More information on this year's winners can be found here.
The number of people who die each year of malaria in India may be 13 times higher than currently estimated, according to a study published online today in The Lancet . As with all estimates of malaria deaths, however, some researchers are skeptical that the new number is valid.
The report, part of the study of death Million Indian government estimates that some 205,000 Indians under age 70 die each year from the disease. Previous World Health Organization (WHO) reports put the figure at 15,000. But many believe that the WHO number is a gross underestimate because it relies primarily on government and health records. Many malaria deaths occur outside hospitals and are therefore not easily registered. And unlike more prolonged diseases, malaria can strike quickly, which makes it even more difficult to follow.
"Something like malaria, which within 48 hours of a patient can actually be in a coma and on their way, they are much more likely to have missed," said Bob Snow, tropical health researcher Kenya medical research Institute, who was not part of the study.
to try to get a better solution to the balance sheet of malaria, the authors of a team of scientists from India, Canada, the UK and sent surveyors selected Favourite States Random regions in India to collect information on deaths that took place there between 01 and 03. As part of these so-called verbal autopsy, investigators asked families and other witnesses to describe what happened victim. They asked if they had suffered a fever, what kind of fever and other issues that could make the switch off malaria. A total of 130 doctors examined the reports, with two each looking.
When the results came back, 3.6% to 75 000 deaths were attributed to malaria. This translates into 205,000 malaria deaths nationwide each year, according to the study, led by Neeraj Dhingra of the national fight against AIDS organization in New Delhi. Ninety percent occurred in rural areas, and 86% occurred outside of any kind of health facility.
But the new figures could be largely exaggerated, said Robert Newman, director of the Global Malaria Programme of WHO, which notes that the use of oral accounts for diagnosing a disease like malaria is incredibly risk. "For a disease that has achieved something that is very distinctive, say a very distinctive rash or paralysis associated with it, you can make a fairly accurate diagnosis through verbal autopsy," he said. "The problem with malaria are the symptoms associated with malaria, especially fever, are very non-specific. So many deaths had fever associated with are not necessarily malaria."
According to Newman, WHO has tested the accuracy of this verbal autopsy in India before. Just 4% of those who claimed to diagnose malaria actually did. "Malaria remains a major public health problem in India," he said, "but I do not think we're talking about a difference of magnitude."
Although verbal autopsies are "a blunt tool," Snow said he still believes The Lancet The paper estimate is legitimate. This is partly because many deaths from slipping through the cracks of the health information systems of India and partly because, at least in terms of geography, the study of statistics correspond to deaths malaria reported by the State. There is also the fact that India is so huge. "A state in India is several African countries," he said.
Snow said a study like this could force scientists to rethink WHO global statistics of malaria, especially in more heavily populated remote regions such as Myanmar, Bangladesh and Pakistan. Newman said the WHO will continue to work with officials of Indian health and examine their data, but stresses that these are things they do regularly.
Meanwhile, snow hope the Indian government will fight against malaria even greater priority, although the fact that the disease is largely concentrated in rural states may attract less attention she.
