OHSU Study Finds Ginkgo Beneficial For MS Symptoms

Daily Science Journal (Sep. 28, 2007) — PORTLAND, Ore. -- When it comes to her health, Janice Winfield of Portland, Ore., does her research.

That's why the stay-at-home mom, who was diagnosed with multiple sclerosis in July 2000, was willing to turn to popular, over-the-counter herbal supplements like ginkgo biloba to deal with memory problems, fatigue and occasional muscle pain.

"I'm definitely interested in alternative medicine," said Winfield, 49, whose form of the neurological disease -- relapsing-remitting MS -- is characterized by frequent symptom flare-ups. Ginkgo "is not only given to someone like me with MS. There's benefit to anyone taking it."

Findings by scientists in the Oregon Health & Science University School of Medicine's Department of Neurology and the OHSU MS Center of Oregon appear to back up that claim. A study presented this month at the American Academy of Neurology's 57th Annual Meeting in Miami Beach, Fla., suggests that ginkgo may be effective in improving attention in MS patients with cognitive impairment. Side effects also were minimal.

The study's lead author, Jesus Lovera, M.D., a research fellow and instructor in neurology, OHSU School of Medicine, said those receiving ginkgo "performed better on a test that measures a person's ability to pay attention and to sort conflicting information."

Of 39 patients completing the study, 20 received ginkgo biloba and 19 received placebo. Researchers found there were no differences in results between the two groups in the areas of gender, education, type of MS, years since onset, or baseline performance on a battery of neuropsychological tests.

But the ginkgo group was four seconds -- about 13 percent -- faster than the placebo group on a timed color and word test that measures attention and such "executive functions" as planning, decision making, and controlling goal-directed behavior and execution of deliberate actions.

During the test, called a "Stroop," patients are shown colored boxes and asked to name the colors. They are then shown the names of colors printed with different-colored inks, such as the word "green" printed in red, and asked to read the word. Finally, patients are asked to describe the ink used for each word.

Lovera said the differences in the Stroop result would be comparable to differences in scores between healthy people ages 30 to 39 and those ages 50 to 59.

Ginkgo appeared to be more beneficial for MS patients having specific problems in the Stroop, so "we would like to do another study in which we choose patients that are impaired in this particular test," Lovera said. "We would also like to test it at higher doses."

Ginko biloba is among several complementary and alternative medicine therapies being investigated by OHSU's Department of Neurology for their effects on symptoms of neurological disease. Studies have ranged from clinical trials of lactoferrin for treating Alzheimer's disease to the use of yoga as a therapy for MS fatigue.

Ginkgo is derived from the leaves of the ginkgo tree, one of the oldest species of trees, and has been used for thousands of years by the Chinese as an herbal remedy for a variety of ailments. It contains potent antioxidants called flavoglycosides that have been shown to have neuroprotective effects in animal models of spinal cord injury. It also has terpene-lactones that block a substance known as platelet activitating factor, which is important in regulating blood vessel function as well as the mediating inflammation and the sticking of inflammatory cells to blood vessels.

Many MS patients have long suspected that ginkgo improves disease symptoms. In a recent survey of 1,913 patients in Oregon, 20 percent reported using the supplement and 39 percent found it to be beneficial. However, until now, there was no evidence the supplement had any effect on memory.

"It has been shown to be of benefit in Alzheimer's, but we did not know if it would work for MS," Lovera said. "We wanted to see if there was any suggestion that it could help patients with MS that are having cognitive problems."

Lovera said the study results demonstrate that ginkgo shouldn't be discounted for treating MS, but its safety and efficacy must be tested in much larger clinical trials before doctors should recommend it to their patients.

"The study suggests that for cognitive problems, it may only help a certain group of patients," he said. "We need to study this further."

And for MS sufferers like Winfield, who participated in the ginkgo study, the herbal supplement will remain one of the many weapons in her arsenal for fighting the disease.

"I would do it again," she said of taking ginkgo. "It could have a benefit for me that I didn't have before." But she emphasizes that "every MS is different, so what might work for me may not work for anybody else. But when it comes to alternative medicine, I'm all for that."


The study was supported by the National MS Society, the National Institutes of Health, the U.S. Department of Veterans Affairs and the Nancy Davis Center Without Walls.


Adapted from materials provided by Oregon Health & Science University.

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Mini Robots To Undertake Major Tasks?

Daily Science Journal (Sep. 25, 2007) — From cell manipulation to micro assembly, micro robots devised by an international team of researchers offer a glimpse of the future.

The MICRON project team, led by the Institute for Process Control and Robotics (IPR), Karlsruhe, Germany, brought together eight international partners. Funded under the European Commission’s FET (Future and Emerging Technologies) initiative of the IST programme, MICRON set out to build a total of five to ten micro robots, just cubic centimetres in size.

“Each one would measure about 1.5cm by 3 cm,” says IPR´s Joerg Seyfried. “They were designed to be complete robots, with different kinds of actuators for gripping, cell manipulation, and so on. Each one would be wireless, with lots of electronics on board, and an infrared control system – rather like a TV remote, but two-way in this case. They would be able to cooperate together on a range of tasks.”

Building the robots involved developing many custom applications, he adds. “One of these was the wireless powering system, the ‘power floor’, which allows the robot to get energy from its surroundings,” he says. “It uses a coil system to transmit the electricity through the air.”

The robots were designed as part of a networked system: “The individual robots are not that intelligent,” explains Seyfried. “They don’t, for example, know where they are, although they know which direction they are moving in. We developed a special positioning system, so that we know where each robot is. It views them from 40 to 50 cm above. They are controlled by a central robot control system, with several networked computers for planning and commands – this could theoretically control many robots.”

The hardest part of the project was “getting the hardware integrated and running – our goal was to have five robots operational, but this couldn’t be done in our three-year timeframe owing to the extreme complexity of the task,” he says.

Nevertheless, the one fully functional robot that the project did achieve could be tested in three different scenarios. “The first was a medical or biological application, in which the robot was handling biological cells, injecting liquid into them,” Seyfried explains. “The second scenario was micro-assembly, in which the robot soldered tiny parts. The final scenario looked at atomic force, with the robot mounting atomic force and doing experiments on it.”

The results were encouraging. “Our experiments showed that the cell injection is entirely feasible, as is the micro soldering,” says Seyfried. Although the MICRON robots are clearly not a mass market product, commercialisation – though still far off – would be perfectly possible, he believes: “Robots with this sort of capability, and mobility, would be perfectly suited to lab work, such as the micro assembly of prototypes. Tasks such as cell injection could be performed on a mass scale.”

With MICRON now having run its course, the project team is currently working on the project reports and evaluation. “What’s missing is the integration work, and this is what we will try to do next within the [also FET-funded] I-Swarm project,” says Seyfried. “This will build on MICRON to produce robots with a ‘swarm’ intelligence – that is, with limited capabilities, but able to communicate with each other.”

The tiny robots of science fiction tales might be smarter, but, as Seyfried points out, “We’re working on the smallest size range currently being worked on by a few other groups worldwide – like MIT. On a European level, MICRON is unique.”

Adapted from materials provided by IST Results.

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Scientists Create Autonomous Robots That Can Stand, Crawl, Wiggle And Even Roll

Daily Science Journal (Sep. 22, 2007) — Wei-Min Shen of the University of Southern California's Information Sciences Institute recently reported to NASA significant progress in developing "SuperBot," identical modular units that plug into each other to create robots that can stand, crawl, wiggle and even roll. He illustrated his comments with striking video of the system in action.

SuperBot modular robotic units self assemble into larger structures, such as this humanoid walker assembly. (Credit: USC Information Sciences Institute)

Shen's presentation took place at the Space Technology and Applications International Forum 2007 (STAIF) held in Albuquerque, New Mexico. For the report, he first offered a description of the SuperBot work:

"Superbot consists of Lego-like but autonomous robotic modules that can reconfigure into different systems for different tasks. Examples of configurable systems include rolling tracks or wheels (for efficient travel), spiders or centipedes (for climbing), snakes (for burrowing in ground), long arms (for inspection and repair in space), and devices that can fly in micro-gravity environment.

"Each module is a complete robotic system and has a power supply, micro- controllers, sensors, communication, three degrees of freedom, and six connecting faces (front, back, left, right, up and down) to dynamically connect to other modules.

"This design allows flexible bending, docking, and continuous rotation. A single module can move forward, back, left, right, flip-over, and rotate as a wheel. Modules can communication with each other for totally distributed control and can support arbitrary module reshuffling during their operation.

"They have both internal and external sensors for monitoring self status and environmental parameters. They can form arbitrary configurations (graphs) and can control these configurations for different functionality such as locomotion, manipulation, and self-repair."

Shen illustrated his words with SuperBot action video showing these processes.

He and his colleagues and students made the fillms in just one week, immediately after completing the mechanics and electronics hardware for the latest batch of SuperBot modules at the beginning of February.

"The fact that SuperBot can achieve so much in so short a time demonstrates the unique value of modular, multifunctional and self-reconfigurable robots," Shen said.

For more information on the SuperBot, see: http://www.isi.edu/robots/superbot.htm

Adapted from materials provided by University of Southern California, via EurekAlert!, a service of AAAS.

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Ginkgo Herbal Supplements Vary Widely In Content

Daily Science Journal (Sep. 21, 2007) — Consumers of Ginkgo biloba herbal products, offered in alternative medicine circles as a remedy for just about everything from dementia to impotence, may not be getting their money's worth, according to a new study by scientists at the University of Idaho. Using a new analytical chemistry technique they developed specifically to examine Ginkgo samples, the researchers found variations of up to tenfold in the Ginkgo products they tested.

"Consumers seldom can be sure exactly what they are buying," says chemistry professor Chen Wai, Ph.D., lead researcher for the study, which was published in the science journal Analytical Chemistry, published by the American Chemical Society.

"The large variation of active ingredients found in Ginkgo biloba products could be a problem for the consumers," the researchers write in the journal article.

Ginkgo products are based on herbal extracts from the leaves of the Ginkgo biloba tree, also known as the maidenhair tree, which first appeared on Earth during the time of the dinosaurs about 200 million years ago. Widely marketed as a way of improving mental alertness and slowing the development of Alzheimer's disease, Ginkgo supplements are among the top selling herbal products in both Europe and the U.S. and have long been a staple of Chinese herbalists.

Chemical substances known as ginkgolides and bilobalide, found in the leaves of the tree, are believed to be the most pharmacologically active compounds, say the researchers. However, they point out, as is the case with many herbal products, the active ingredients are usually present in only trace amounts along with large quantities of other compounds. Determining the amount of ginkgolides and bilobalide in Ginkgo products generally is a time-consuming and tedious process, which has added to the difficulty of establishing efficient quality control programs for the products, claim the researchers.

"The lack of simple and reliable separation and analytical processes for herbal products is probably a major cause of the quality-related problems found in the herbal medicine market today," according to the researchers.

The process developed by Wai and colleague Qingyong Lang could help solve that problem by reducing the time required to separate the active ingredients from hours to just a few minutes. It essentially involves boiling the leaves of the tree, or Ginkgo extract products, to separate the ginkgolides and bilobalide and then using a common analytical instrument called a gas chromatograph to measure the compounds.

"Compared to other reported methods for ginkgolide separation, this method can significantly reduce the operation time," say the researchers. "The principle of this analytical method may also be applied to other medicinal herbs," they add.

Adapted from materials provided by American Chemical Society.

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Pros And Cons Of Antioxidants From Fruits And Vegetables

Daily Science Journal (Sep. 19, 2007) — Nutrition: It's not just the four basic food groups any more.

Researcher Dr. Susanne Mertens-Talcott of Texas A&M University is looking into how plant-based phytochemicals, including antioxidants and herbal supplements, can be useful in the promotion of health and prevention of chronic diseases.

This field is still growing. In the U.S. more than $20 billion was spent on dietary supplements in 2005, said Talcott, who is in a joint research and teaching position with the department of nutrition and food science and the department of veterinary physiology and pharmacology.

"Over $7 billion was spent on herbal dietary supplements in 2005." These supplements are plant-based, including grape seed extract, St. John's wort, ginseng and biloba extract, she added. "In addition to that there is the segment of so-called ‘functional foods,' including antioxidant foods – for example, fruit juices and beverages and grain-based products," Talcott said.

The amount spent on these foods each year "has increased drastically; however, we do not know yet how efficacious these different antioxidants really are in the prevention of chronic diseases such as cardiovascular disease and cancer," she said. "We also do not know very much about the mechanisms, which appear to include antioxidant and anti-inflammatory effects of these phytochemicals."

This can be important to health since these reactive oxygen species or ‘free radicals' may play a role in some diseases, including Alzheimer's, cancer and atherosclerosis, she said.

"However, other mechanisms, including the prevention of chronic inflammation and interaction with intracellular mechanisms, may be as important in the prevention of chronic diseases," she said. But are they safe? Are they efficient? How much is required? And how much is too much? Talcott is looking for the answers to these questions through her research.

"My overall goal is to find out more about the safety and efficacy of phytochemical dietary supplements," she said. Because these items are already popular with consumers, "we need to follow up with research. We know very little about (dose) recommendations and how safe (they are)."

Phytochemicals, also called secondary plant compounds – including antioxidants – have been defined as chemicals found in plants that have protective or disease-fighting properties.

Pomegranate juice and extract have been the focus of much of her studies. Because these are used in different food products, they are found as ingredients in many different items in supermarkets, Talcott said.

She has also done research on the properties of muscadine grapes and acai, a palm fruit from Brazil, as well as isolated compounds including quercetin and ellagic acid, which are also sold as dietary supplements.

The results of some of her studies were published in the Oct. 13, 2006, edition of the Journal of Agricultural and Food Chemistry. The article was titled "Absorption, Metabolism and Antioxidant Effects of Pomegranate (Punica granatum L.) Polyphenols after Ingestion of a Standardized Extract in Healthy Human Volunteers."

In addition to her research, Talcott teaches a class on "Special Topics in Phytochemicals of Fruits and Vegetables" for students who are majoring in nutrition and food science. Many of the students are planning to enter medical or pharmacy school, she added.

"It is my goal to give students as much relevant information, which they directly can apply in their desired profession," Talcott said. "Consumers and patients have many questions about herbal dietary supplements, and health care professionals and (members of the) food industry are and will be even more confronted with these questions."

For example, Dr. Joseph M. Betz was a recent guest lecturer in Talcott's class. Betz is the director of the Dietary Supplement Methods and Reference Materials Program Office of Dietary Supplements at the National Institutes of Health in Bethesda, Md. He discussed Food and Drug Administration rules as to the differences between foods and drugs and how each must be labeled. With regard to herbal supplements, this can sometimes be a little tricky, he said.

During the question and answer period at the end of his talk, one of the students asked about a recent study on antioxidants. According to news reports, the study seemed to find that antioxidants – especially vitamins A and E – don't have the beneficial properties they are thought to have and may even increase mortality.

Talcott offered this clarification in regard to the study: "This study statistically analyzed many different clinical studies with vitamins A, E (and) C, beta-carotene and selenium. The performed statistical analysis indicated that vitamin A and E and beta-caraotene may increase mortality in some of the selected studies. The meaning of this study currently is being discussed."

The study looked at synthetic antioxidants, she said, which are not the same compounds that she is researching. "Even though we still have a lot to learn about the efficacy, safety and dosing recommendations for herbal supplements and antioxidant foods, we can be confident to recommend a healthy balanced diet according to the food-pyramid rich in fresh fruits and vegetables. I also would not see a problem with the intake of reasonable amounts of standardized high-quality antioxidant dietary supplements," she said

"It is my long-term goal to see science-based intake recommendations developed for those herbal plant compounds which have a proven potential in the promotion of health and prevention of chronic disease."

Adapted from materials provided by Texas A&M University - Agricultural Communications.

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Potential New Way Of Treating Inflammatory Diseases Identified

Daily Science Journal (Sep. 19, 2007) — Scientists have shown for the first time that platelets, the cells needed for blood clotting, help white blood cells called neutrophils fight inflammation.

The discovery was made by Ralph Kettritz, Professor of Medicine at the Medical Faculty of the Charite and investigator at the Max Delbrueck Center for Molecular Medicine, Berlin, Germany, and colleagues. The results of the study could lead to new anti-inflammatory compounds for the treatment of inflammatory vascular injury.

"We found an entirely new mechanism by which neutrophils induce inflammation," Kettritz says. "So far, scientists have shown that platelets form clots and neutrophils can cause symptoms of inflammation, such as swelling, redness, and heat. In this study, we show that platelets and neutrophils sometimes work together to heal a wound or fight an infection."

During inflammation -- a protective reaction from the tissues following a wound or infection -- white blood cells attack bacteria and platelets form clots that close any potential wound. White blood cells called neutrophils are the first to launch an attack against the bacteria. They are attracted by substances, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), that are released at the early stages of inflammation. Once activated, neutrophils engulf and destroy bacteria and damaged tissue.

In addition to neutrophils, two other types of white blood cells, called macrophages and lymphocytes, also engage in the fight against bacteria. These cells are activated by a chemical compound called tumor necrosis factor (TNF) released by the neutrophils. Although there are several ways by which neutrophils release TNF, Kettritz and colleagues found that neutrophils can be stimulated to produce TNF in a totally new and different way.

"Usually, TNF is produced when specific chemicals bind to proteins called receptors on the surface of a neutrophil, which tells the cell that it should make TNF," Kettritz says. "This time, we found that a neutrophil can acquire receptors that are not already present on its surface and use them to stimulate the production of TNF."

The receptors, called GPIIb/IIIa, are sent to neutrophils by platelets. Like a letter sent in an envelope, these receptors are packaged in vesicles called microparticles that, when they reach a neutrophil, bind to its surface and release the receptors. Once released, the receptors are incorporated into the neutrophil's cell membrane.

Kettritz and his team also found that these newly-acquired receptors did not work alone. To stimulate neutrophils to produce TNF, the GPIIb/IIIa receptor works in tandem with the receptor for GM-CSF (the substance produced during the early stages of inflammation). The scientists found that the neutrophil produces TNF both when GPIIb/IIIa binds to a protein outside the cell called fibronectin and when the GM-CSF receptor binds to GM-CSF.

"We have shown for the first time that platelets can, by using microparticles, help other cells -- in this case, neutrophils -- respond to inflammation," Kettritz says. "We also found for the first time that receptors involved in blood clotting also trigger an inflammatory response."

These results may help devise new drugs against several types of inflammation by targeting the GPIIb/IIIa receptors acquired by neutrophils. In particular, drugs currently used to prevent blood clotting by inhibiting GPIIb/IIIa receptors on platelets may be used against inflammation.

Kettritz and colleagues tested three of these drugs -- abciximab, epifibatide, and tirofiban -- on cell cultures in which neutrophils had received the GPIIb/IIIa receptors from platelets and confirmed the drugs' effects on inflammation. The scientists showed that all three drugs inhibited the production of TNF, which reduced inflammation in these cells. These results also led the researchers to speculate that some of the beneficial effects of the three drugs on patients with acute coronary syndrome result from their anti-inflammatory properties.

If the drugs' effects are confirmed in clinical trials, they could be used against several types of inflammation that include acute vasculitis, an inflammation of blood vessels that can affect any organ in the body. Also, the drugs have been used successfully to treat acute coronary syndrome, which refers to certain types of heart attack and unstable angina. The new results show that these beneficial effects may be due not only to their anti-clotting properties, but also to their anti-inflammatory qualities.

"The results of this study are very encouraging," Kettritz says. "Although specific drugs that target GPIIb/IIIa receptor actions on neutrophils may need to be developed in the future, these three drugs can now be tested in clinical trials, which could make them -- or modified versions of them -- new anti-inflammatory drugs."

The new study, to be published in the September 21 issue of the Journal of Biological Chemistry, was selected as a "Paper of the Week" by the journal's editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.

Article: "Beta 2-integrins and acquired GPIIb/IIIa receptors cooperate in NF-KB activation of human neutrophils," by Birgit Salanova, Mira Choi, Susanne Rolle, Maren Wellner, Friedrich C. Luft, and Ralph Kettritz

Adapted from materials provided by American Society for Biochemistry and Molecular Biology, via EurekAlert!, a service of AAAS.

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Consumption Of Green Tea Associated With Reduced Mortality In Japanese Adults, Drinking Tea Associated With Lower Risk Of Ovarian Cancer

Daily Science Journal (Sep. 13, 2007) — Adults in Japan who consumed higher amounts of green tea had a lower risk of death due to all causes and due to cardiovascular disease, according to a study in the September 13 issue of JAMA. But there was no link between green tea consumption and a reduced risk of death due to cancer.

Tea is the most consumed beverage in the world aside from water. Three billion kilograms of tea are produced each year worldwide, according to background information in the article. Because of the high rates of tea consumption in the global population, even small effects in humans could have large implications for public health. Among teas, green tea polyphenols have been extensively studied as cardiovascular disease (CVD) and cancer chemopreventive agents. Although substantial evidence from in vitro and animal studies indicates that green tea preparations may impede CVD and carcinogenic processes, the possible protective role of green tea consumption against these diseases in humans remains unclear.

Shinichi Kuriyama, M.D., Ph.D., of the Tohoku University School of Public Policy, Sendai, Japan, and colleagues examined the association between green tea consumption and mortality (death rate) due to all causes, CVD, and cancer within a large population. The study, initiated in 1994, included 40,530 adults (age 40 to 79 years) in northeastern Japan, where green tea is widely consumed. Within this region, 80 percent of the population drinks green tea and more than half of them consume 3 or more cups and day. The participants, who had no history of stroke, coronary heart disease, or cancer at baseline, were followed for up to 11 years (1995-2005) for all-cause death and for up to 7 years (1995-2001) for cause-specific death.

Over 11 years of follow-up, 4,209 participants died, and over 7 years of follow-up, 892 participants died of cardiovascular disease and 1,134 participants died of cancer. The researchers found that green tea consumption was inversely associated with death due to all causes and due to cardiovascular disease. Compared with participants who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a risk of all-cause mortality and CVD mortality that was 16 percent lower (during 11 years of follow-up) and 26 percent lower (during 7 years of follow-up), respectively.

These inverse associations of all-cause and CVD mortality were stronger among women, although the inverse association for green tea consumption was observed in both sexes. In women, compared with those who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a 31 percent lower risk of CVD death.

The researchers found there no significant association between green tea consumption and death from cancer. There were weak or neutral relationships between black tea or oolong tea and mortality.

"Clinical trials are ultimately necessary to confirm the protective effect of green tea on mortality," the authors write.

This study was supported by a Health Sciences Research Grant for Health Services, Ministry of Health, Labour, and Welfare, Japan.

Adapted from materials provided by JAMA and Archives Journals, via EurekAlert!, a service of AAAS.

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Drinking Tea Associated With Lower Risk Of Ovarian Cancer

Women who drank at least two cups of tea a day had a lower risk of ovarian cancer than those who did not drink tea, according to a study in the December 12/26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Evidence from laboratory studies indicates that green and black tea preparations may protect against various cancers. But few epidemiological studies have examined the relationship specifically between tea consumption and the risk of ovarian cancer, according to background information in the article.

Susanna C. Larsson, M.Sc., and Alicja Wolk, D.M.Sc., of the National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, prospectively examined the association between tea consumption and the risk of ovarian cancer in 61,057 women, aged 40 to 76, who were participants in the population-based Swedish Mammography Cohort. Participants completed a validated 67-item food frequency questionnaire at enrollment between 1987 and 1990, and were followed for cancer incidence through December 2004. At baseline, 68 percent of the participants reported drinking tea (mainly black tea) at least once per month. During an average follow-up of 15.1 years, 301 women were diagnosed as having invasive epithelial ovarian cancer.

"We observed a 46 percent lower risk of ovarian cancer in women who drank two or more cups of tea per day compared with non-drinkers," the authors report. "Each additional cup of tea per day was associated with an 18 percent lower risk of ovarian cancer."

Women who drank less than one cup of tea per day had an 18 percent lower risk of ovarian cancer than non-drinkers. The risk was 24 percent lower for women who drank one cup of tea per day.

"This association does not depend on lower coffee consumption among women with high tea consumption; coffee is not associated with ovarian cancer risk in this cohort," the authors write.

"In summary, our results from a large population-based cohort of Swedish women suggest that tea consumption may lower the risk of ovarian cancer," the authors conclude. "Because prospective data on this relationship are scarce, our findings need confirmation by future studies."

(Arch Intern Med. 2005;165:2683-2686. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This work was supported by research grants from the Swedish Cancer Foundation and the Swedish Research Council/Longitudinal Studies, Stockholm, Sweden.


Adapted from materials provided by JAMA and Archives Journals, via EurekAlert!, a service of AAAS.

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Migraines: Options To Prevent And Treat The Pounding Pain

Daily Science Journal (Sep. 12, 2007) — Migraines are more than a bad headache. As nearly 30 million Americans can attest, the throbbing pain of a migraine can be debilitating, lasting from a few hours to several days. The condition can be aggravated by light, sounds, odors, exercise, even routine physical activities. Nausea, with or without vomiting, may occur.

Nearly 30 million Americans suffer from migraines. (Credit: iStockphoto/Guillermo Perales Gonzalez)

Fortunately, treatment helps most people who have migraines.

Doctors may recommend preventive medications for patients who have two or more debilitating episodes a month. Typically the medication is taken at regular intervals, often daily. Antidepressants, anti-seizure medications and cardiovascular drugs may help prevent migraines.

Infrequently, nonprescription nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin, others) or naproxen sodium (Aleve, others) may help. Injections of botulinum toxin type A (Botox) is an alternative for people who can’t take or don’t respond well to preventive medications. However, this use of Botox for migraine prevention is not approved by the Food and Drug Administration.

Pain relief drugs for migraines should be taken as soon as symptoms begin. Mild migraines may respond to NSAIDs or aspirin. A moderate migraine may respond to a nonprescription combination of a drug containing acetaminophen, aspirin and caffeine. Other drug categories used to treat pain include triptans, which mimic the action of the brain chemical serotonin; anti-nausea and related drugs; and ergots, which were used for decades before the more recent introduction of triptans.

Some patients find relief from alternative therapies. The National Institutes of Health has concluded that acupuncture may help control headaches. A study in the journal Headache showed that a combination of yoga, breathing exercises and relaxation techniques reduces migraine frequency and pain.

Some find benefit in herbal remedies, such as butterbur, which appears to be safe if taken for a short period to prevent migraines. In addition, the supplement coenzyme Q10 appears to reduce migraine frequency for some. Patients who consider alternative therapies should consult their physician about the pros and cons and to prevent any drug interactions.

The September issue of Mayo Clinic Health Letter provides more information on treatments to prevent migraines and stop the pain.

Adapted from materials provided by Mayo Clinic, via Newswise.

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Cluster And Double Star Uncover More On Bright Aurorae

Daily Science Journal (Sep. 12, 2007) — Cluster data has helped provide scientists with a new view of magnetospheric processes, challenging existing theories about magnetic substorms that cause aurorae and perturbations in GPS signals.

The diagram shows all 11 spacecraft of the Cluster, Double Star and THEMIS missions orbiting the Earth. All three missions are studying the environment of Earth's magnetosphere. (Credit: ESA)

The onset of magnetic substorms that originate in Earth’s magnetosphere has been explained by two competing models: current disruption and near-earth reconnection. Current beliefs have been challenged using data from ESA’s Cluster satellites, and CNSA’s Double Star, a mission with ESA participation. Recent research suggests a third type of substorm onset.

Magnetic substorms often cause bright and colourful aurorae at high latitudes, in places such as Scandinavia or Canada. These aurorae are caused by energetic electrons that spiral down Earth’s magnetic field lines and collide with atmospheric atoms at an altitude of about 100 km. The energetic electrons come from the magnetotail, located on the nightside of Earth where the solar wind stretches Earth’s magnetic field lines into a long tail.

At the centre of the magnetotail is a denser region known as the plasma sheet. Plasma is a gas composed of ions and electrons which is electrically neutral. It is spread over large distances in space and guided by the action of magnetic and electric fields. A substorm induces violent changes in the plasma sheet. It energises ions and electrons and hurls them Earthward. The substorm itself can occur as a series or in isolation.

Apart from producing the beautiful show of light, substorms also excite a large portion of Earth's ionosphere, perturbing the reception of GPS signals and communication between Earth and orbiting satellites. Despite decades of space research, the mechanism causing the onset of substorms remains a mystery.

There are three events associated with the onset of a substorm: auroral brightening, current disruption, and magnetic reconnection.

Auroral brightening is a sudden change of the aurora from light grey to very bright and colourful auroras at an altitude of about 100 km, visible from ground. Current disruption occurs at a height of roughly 60 000 km on the nightside or at a sixth of the distance to the Moon and is associated with turbulent fluctuations in the magnetic field.

Magnetic reconnection is the process whereby magnetic field lines from different magnetic domains collide and reconnect, heating and accelerating plasma. It occurs at around a third of the distance to the Moon or at a height of 120 000 km, in a thin plane close to the magnetic equator of the magnetotail.

The difference between the two existing theories on magnetic substorms is that they differ on the order in which the events take place.

Prof Sergeev (St Petersburg State University, Russia) and colleagues from Europe, the USA and China studied three consecutive substorm onsets, from data collected on board Cluster and Double Star on 26 September 2005. For the first time, data indicate that the current disruption process and magnetic reconnection can coincide in space and time showing, possibly, two sides of the same process.

They also found that in this case, magnetic reconnection occurred closer to the Earth than usual, almost co-located with the current disruption process, between 60 000 and 90 000 km. Related localised auroral brightenings were captured few tens of seconds later by an ultra violet imager onboard the NASA’s IMAGE satellite.

“Cluster’s multipoint measurements and the spatial coverage possible together with Double Star have been instrumental in making these unique observations possible,” commented Sergeev.

In February 2007, NASA launched THEMIS, a five-satellite mission dedicated to the study of the onset of substorms. "With the many scientific satellites in orbit, we have a never-before opportunity to study the global solar-magnetospheric environment and the physical processes involved," said Philippe Escoubet, Cluster and Double Star project scientist of the European Space Agency.

The results appear in ‘Observation of repeated intense near-Earth reconnection on closed field lines with Cluster, Double Star and other spacecraft’ by V. Sergeev, V. Semenov, M. Kubyshkina, V. Ivanova, W. Baumjohann, R. Nakamura, T. Penz, A. Runov, T. L. Zhang, K. Glassmeier, V. Angelopoulos, H. Frey, J. Sauvaud, P. Daly, J. Cao, H. Singer, and E. Lucek. The paper is published in the 20 January 2007 issue of the Geophysical Research Letters.

Adapted from materials provided by European Space Agency.

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Reading Process Is Surprisingly Different That Previously Thought, Technology Shows

Daily Science Journal (Sep. 11, 2007) — Being able to read competently is one of the most important skills we need to function in today’s fast-paced society. Analysing the way we read can offer valuable insights into how we process visual information.

When we read, our eyes look at different letters in the same word and then combine the different images through a process known as fusion, researchers have found. (Credit: iStockphoto/Shannon Long)

Scientists have been interested in the movements of our eyes while reading for forty years. However, until now most assumed that when we read both eyes look at the same letter of a word concurrently.

Now ground-breaking research by cognitive psychologist Professor Simon Liversedge and his team at the University of Southampton has shown that this is not actually the case. They found that our eyes are actually up to something much more exciting when we read - our eyes look at different letters in the same word and then combine the different images through a process known as fusion.

The research Prof. Liversedge will present at the BA Festival of Science in York shows that the reading process is not as simple as one might think; it is rarely a case of the eyes scanning the page smoothly from left to right. Depending on what we are reading and how hard we are finding the information to digest our eyes make small jerky movements, that allow us to focus on a particularly difficult word or often re-read passages we didn’t get the first time. Analysing these eye movements enables psychologists to understand how our brain processes the sentence.

With sophisticated eye tracking equipment able to determine which letter of a font-size 14 word a person is looking at every millisecond from 1 metre away, Prof. Liversedge’s team went one further and looked at the letters within the word within the sentence. They were able to deduce that when our eyes are not looking at the same letter of the word, they are usually about two letters apart. Prof. Liversedge explains: ‘Although this difference might sound small, in fact it represents a very substantial difference in terms of the precise "picture" of the world that each eye delivers to the brain.'

So if our eyes are looking at different parts of the same word, thereby receiving different information from each eye, how is it that we are able to see the words clearly enough to read them? There are two ways the brain can do this; either the image from one of the eyes is blocked or the two different images are somehow fused together. To test how the latter mechanism might work, the team chose words that could easily split in two, such as cowboy, and presented half of the word to the left eye, and half to the right eye separately. They then analysed readers’ eye movements when reading sentences containing these particular words presented in this way.

‘We were able to clearly show that we experience a single, very clear and crisp visual representation due to fusion of the two different images from each eye,’ he explains. ‘Also when we decide which word to look at next we work out how far to move our eyes based on the fused visual representation built from the disparate signals of each eye.

‘A comprehensive understanding of the psychological processes underlying reading is vital if we are to develop better methods of teaching children to read and offer remedial treatments for those with reading disorders such as dyslexia. Our team are now measuring the range of visual disparities over which both adult and child readers can successfully fuse words.’

Professor Simon Liversedge will give his talk, ‘What our eyes get up to while we read’ as part of the session entitled ‘What eye movements tell us about the brain and language’ on 14 September at Vanbrugh V/045, University of York as part of the BA Festival of Science.

Adapted from materials provided by British Association for the Advancement of Science.

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Cell Phones Should Be Kept Away From Hospital Beds, Dutch Experts Say

Daily Science Journal (Sep. 9, 2007) — Cell phones should come no closer than one meter to hospital beds and equipment, according Dutch research published in the online open access journal, Critical Care. Scientists demonstrated that incidents of electromagnetic interference (EMI) from second and third generation mobile phones occurred even at distance of three meters.

Hazardous incidents of electromagnetic interference from second and third generation mobile phones varied from a total switch off and restart of mechanical ventilator and complete stops without alarms in syringe pumps to incorrect pulsing by an external pacemaker. (Credit: iStockphoto/Bakaleev Aleksey)

In this particular study, the research team examined the effects of General Packet Radio Service (GPRS) and Universal Mobile Telecommunications System (UMTS) signals on critical care equipment such as ventilators and pacemakers. Almost 50 EMI incidents were recorded; 75% were significant or hazardous. Hazardous incidents varied from a total switch off and restart of mechanical ventilator and complete stops without alarms in syringe pumps to incorrect pulsing by an external pacemaker.

The second generation (2.5G) GPRS signal caused the highest number of EMI incidents at over 60% whereas the third generation (3G) UMTS signal was responsible for just 13%. EMI incidents also occurred a greater distance with GPRS with a hazardous incident even at three meters.

While first generation mobile phones are used mainly for voice transmission, 2.5G and 3G phones enable internet access, sending and receiving data. They entered the market, however, with little proof regarding their safe use in the medical environment.

Dr Erik van Lieshout, lead researcher from the Academic Medical Center, University of Amsterdam, said; "Our work has real implications for present hospital restrictions of mobile phone use in patient areas."

"It is unlikely that mobile phone induced EMI in hospitals will be eradicated in the near future so the one meter rule currently in place should continue, as it is relatively safe," commented Dr van Lieshout.

Article: "Interference by new generations mobile phones on critical care medical equipment," Erik Jan van Lieshout, Sabine N van der Veer, Reinout Hensbroek, Johanna C Korevaar, Margreeth B Vroom and Marcus J Schultz, Critical Care (in press)

Adapted from materials provided by BioMed Central, via EurekAlert!, a service of AAAS.

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First Diploid Human Genome Sequence Shows We're Surprisingly Different

Daily Science Journal (Sep. 4, 2007) — Researchers at the J. Craig Venter Institute (JCVI), along with collaborators at The Hospital for Sick Children (Sick Kids) in Toronto and the University of California, San Diego (UCSD), have published a genome sequence of an individual, J. Craig Venter, Ph.D., that covers both of his chromosome pairs (or diploid genome), one set being inherited from each of his parents.

Spectral karyotype analysis. (Credit: J. Craig Venter Institute)

Two other versions of the human genome currently exist—one published in 2001 by Dr. Venter and colleagues at Celera Genomics, and another at the same time by a consortium of government and foundation-funded researchers. These genomes were not of any single individual, but rather were a mosaic of DNA sequences from various donors. In the case of Celera it was a consensus assembly from five individuals, while the publicly-funded version was based on patching together sequences from over 100 anonymous human sources. Both versions greatly underestimated human genetic diversity.

This new genome (called “HuRef”) represents the first time a true diploid genome from one individual—Dr. Venter, has been published. The research is available in the open access public journal, PLoS Biology.

Researchers at the JCVI have been sequencing and analyzing this version of Dr. Venter’s genome since 2003. Building on reanalyzed data from Dr. Venter’s genome that constituted 60% of the previously published Celera genome, the team had the goal of constructing a definitive reference human genome based on one individual. Using whole genome shotgun sequencing and highly accurate DNA sequencing using Sanger-based chemistry, the team produced additional data which constitutes the final 32 million sequence reads.

From the combined data of more than 20 billion base pairs of DNA, the team was able to assemble the majority of Dr. Venter's genome. Since this genome assembly uniquely catalogues the contributions of each of the parental chromosomes, for the first time the amount of variation existing between the two could be determined. Surprisingly, a higher than expected amount of genetic variation was found to exist between the two human chromosomes.

“Each time we peer deeper into the human genome we uncover more valuable insight into our intricate biology,” said Dr. Venter. “With this publication we have shown that human to human variation is five to seven-fold greater than earlier estimates proving that we are in fact more unique at the individual genetic level than we thought.” He added, “It is clear however that we are still at the earliest stages of discovery about ourselves and only with additional sequencing of more individual genomes will we garner a full understanding of how our genes influence our lives.”

Within the human genome there are several different kinds of DNA variants. The most studied type is single nucleotide polymorphisms or SNPs, which are thought to be the essential variants implicated in human traits and disease susceptibility. A total of 4.1 million variants covering 12.3 million base pairs of DNA were uncovered in this analysis of Dr. Venter’s genome. Of the 4.1 million variations between chromosome sets, 3.2 million were SNPs. This is a typical number expected to be found in any other human genome, but there were at least 1.2 million variants that had not been described before. Surprisingly, nearly one million were different kinds of variants including: insertion/deletions (“indels”), copy number variants, block substitutions and segmental duplications.

While the SNP events outnumbered the non-SNP variants, the latter class involved a larger portion (74%) of the variable component of Dr. Venter's genome. This data suggests that human-to-human variation is much greater than the 0.1% difference found in earlier genome sequencing projects. The new estimate based on this data is that genomes between individuals have at least 0.5% total genetic variation (or are 99.5% similar) The researchers suggest that much more research needs to be done on these non-SNP variants to better understand their role in individual genomics.

According to Samuel Levy, Ph.D., lead author and senior scientist at JCVI, “The ability to use unbiased, high throughput, sequencing methods coupled with advance computational analytic methods, enables us to characterize more comprehensively the wide variety of individual genetic variation. This offers us an unprecedented opportunity to study the prevalence and impact of these DNA variants on traits and diseases in human populations.”

Another important feature that is made possible by having an individual, diploid genome is the ability to generate more informed haplotype assemblies. Haplotypes are groups of linked variations along the chromosomes. Other studies have generated many common haplotypes, however these are based on averages of large populations rather than individuals. Individual haplotypes enable scientists to study rare or 'private' variants that might explain and help predict traits and diseases in that particular person—allowing an individualized approach in genomic applications.

In the HuRef analysis, the team used the heterozygous portion of the 4.1 million variant set and new algorithms to build haplotype assemblies. These haplotype assemblies were typically an order of magnitude larger than what can be achieved by genotyping a single individual, with over half the genome contained in segments greater than 200,000 base pairs in length. The JCVI researchers expect this number to improve significantly as additional sequence coverage is added to HuRef using a variety of new sequencing technologies.

"In the future it will be possible to know the parental origin of DNA that is contributing, either alone or in combination, to various traits or disease," said co-author Stephen Scherer, Ph.D., senior scientist in Genetics and Genomic Biology at SickKids and professor of Molecular and Medical Genetics at the University of Toronto. "This study discovered that in an individual genome upwards of 44% of genes were variable in sequence, a number that geneticists have wondered about for 50 years. With this type of knowledge now in hand, the stage is set for an era of personalized medicine where genome sequence information becomes a critical reference to assist with health-related decisions", concluded Scherer.

Background

The publication of Dr. Venter’s genome represents the first publication of an individual’s genome and the first human genome publication since the first sequence and analysis of the human genome published in Science in 2001 by Dr. Venter and colleagues at Celera Genomics. The publicly funded genome project also published their version of the human genome at the same time in the journal Nature. At Celera there were five individuals whose genomes were used for that consensus human genome assembly. One of those individuals was Dr. Venter whose DNA constituted the majority of the DNA for that genome. The publicly funded genome project used DNA from a variety of individuals and is a composite version.

The new HuRef version of the human genome is the sequence and assembly of one individual in which the person’s two sets of chromosomes (one inherited from the mother and one set from the father) are represented. It is this kind of genome sequencing and analysis that will usher in the true era of individualized medicine.

Dr. Venter and the team at JCVI have long been proponents of finding new and improved methods for sequencing genomes since it is only through cost-effective and accurate sequencing methods that millions of human genomes can be sequenced. In September 2003, the JCVI announced a $500,000 prize for advances leading to the sequencing of one genome for $1,000 or less. The JCVI prize was eventually joined with the $10 million Archon X Prize for Genomics.

For the HuRef project, the team at JCVI used a more traditional method of sequencing—whole genome shotgun assembly which is built upon Sanger dideoxy sequencing. Then, Applied Biosystems 3730xl high-throughput DNA sequencing machines were employed since these methods still produce the longest and most accurate lengths of DNA. This project was designed to produce an accurate and more complete version of a single individual’s genome rather than producing a fast and potentially less expensive version. From the HuRef genome however the researchers believe that newer methods for sequencing can be used to enable more people to have their genome’s sequenced and analyzed. It is clear that the HuRef version is likely the last time that these more traditional methods of sequencing will be employed.

Funding for the research on the new HuRef diploid genome was from the J. Craig Venter Institute.

Adapted from materials provided by J. Craig Venter Institute.

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Pomegranate Fruit Shown To Slow Cartilage Deterioration In Osteoarthritis

Daily Science Journal (Sep. 1, 2007) — Pomegranate fruit extracts can block enzymes that contribute to osteoarthritis according to a Case Western Reserve University School of Medicine study published in the September 2005 issue of the Journal of Nutrition.

The study looked at the ability of an extract of pomegranate fruit against Interleukin-1b (IL-1b), a pro-inflammatory protein molecule that plays a key role in cartilage degradation in osteoarthritis. Current treatments for osteoarthritis -- which affects 20 million people nationwide, according to the National Institutes of Health -- offer limited effectiveness and do little to slow joint destruction and disease progression.

"This has generated considerable interest in the identification and development of new approaches and reagents to treat and inhibit, if not abolish, the progress of the disease," said Tariq M. Haqqi, Ph.D., professor of medicine at Case.

"Arthritis is one of the foremost diseases for which patients seek herbal or traditional medicine treatments. However, all the extracts and herbs have not yet been scientifically evaluated for their efficacy and safety. Indeed, some of them may even interfere with the current treatments," Haqqi said. "Therefore, careful use of supplements and herbal medicines during early stages of disease or treatment may be made to limit the disease progression."

Plant-based flavonoids found in fruits, leaves and vegetables have attracted a lot of attention for their beneficial health effects in various diseases. Pomegranate, in particular, has been found to possess antioxidant and anti-inflammatory properties that have potential therapeutic benefits in a variety of diseases. The Case study demonstrated for the first time the ability of pomegranate fruit extracts to slow the deterioration of human cartilage.

"It has been revered through the ages for its medicinal properties," said Haqqi. "Studies in animal models of cancer suggest that pomegranate fruit extract consumption may be anticarcinogenic, whereas studies in mice and humans indicate that it may also have a potential therapeutic and chemopreventive adjuvant effect in cardiovascular disorders."

A bonus with the native Persian fruit is that its antioxidant constituents are rapidly absorbed by the body and are non-toxic.

Using tissue samples of human cartilage affected by osteoarthritis, researchers added a water extract of pomegranate fruit to the culture using a well-established in vitro model. The findings showed a new activity for pomegranate fruit extract -- namely cartilage protection -- in addition to its previously discovered antioxidant and anti-inflammatory properties.

The IL-1b protein molecules create an overproduction of inflammatory molecules including matrix metalloproteases (MMP), which are tightly regulated enzymes necessary for tissue remodeling. When overproduced in a disease state, such as osteoarthritis, they degrade the cartilage resulting in joint damage and destruction.

The Case study results indicate that pomegranate fruit extracts inhibit the overproduction of MMP enzymes in human cartilage cells.

"This suggests that consumption of pomegranate fruit extract may help in protecting cartilage from the effects of IL-1b by suppressing cartilage degradation in OA," Haqqi said.

More studies are needed to determine the absorption rate of pomegranate fruit extracts in the joints. Future plans include animal model studies in osteoarthritis to determine whether the fruit extract promotes cartilage repair, and whether it can also be effective in treating rheumatoid arthritis.

This research was supported in part by grants from the National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases and from the National Center for Complementary and Alternative Medicine.

Adapted from materials provided by Case Western Reserve University, via EurekAlert!, a service of AAAS.

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