ROBOT MAKES SCIENTIFIC DISCOVERY ALL BY ITSELF

From the FMS Global and UK News Desk of Jeanne Hambleton

Courtesy NewsGatorNews

By Lizzie (iamlizzieee@yahoo.com) – April 02, 2009
Categories: Artificial Intelligence, Robotics, Science Tools, Web/Tech

For the first time, a robotic system has made a novel scientific discovery with virtually no human intellectual input.

Scientists designed “Adam” to carry out the entire scientific process on its own: formulating hypotheses, designing and running experiments, analyzing data, and deciding which experiments to run next.

“It’s a major advance,” says David Waltz of the Center for Computational Learning Systems at Columbia University.

“Science is being done here in a way that incorporates artificial intelligence. It is automating a part of the scientific process that has not been automated in the past.”

The demonstration of autonomous science breaks major ground. Researchers have been automating portions of the scientific process for decades, using robotic laboratory instruments to screen for drugs and sequence genomes, but humans are usually responsible for forming the hypotheses and designing the experiments themselves. After the experiments are complete, the humans must exert themselves again to draw conclusions.

Meanwhile, some software programs can analyze data to generate hypotheses or conclusions, but they do not interact with the physical realm. Adam is the first automated system to complete the cycle from hypothesis, to experiment, to reformulated hypothesis without human intervention.

Adam’s British designers, led by Ross King at Aberystwyth University in Wales, acknowledge that the robot’s discoveries have been “of a modest kind” thus far.

Its proving ground as a scientist has been the genome of baker’s yeast, a popular laboratory species. Baker’s yeast is one of the best understood organisms, but 10 to 15 percent of its roughly 6,000 genes have unknown functions. The scientists hoped Adam could shed light on some of these mystery genes.

They armed Adam with a model of yeast metabolism and a database of genes and proteins involved in metabolism in other species. Then they set the mechanical beast loose, only intervening to remove waste or replace consumed solutions. The results appear Thursday in Science.

Adam sought out gaps in the metabolism model, specifically orphan enzymes, which scientists think exist, but which have not been linked to any parent genes. After selecting a desirable orphan, Adam scoured the database for similar enzymes in other organisms, along with the corresponding genes. Using this information, it hypothesized that similar genes in the yeast genome may code for the orphan enzyme.

The process might sound simple — and indeed, similar “scientific discovery” algorithms already exist — but Adam was only getting started. Still chugging along on its own, it designed experiments to test its hypotheses, and performed them using a fully automated array of centrifuges, incubators, pipettes, and growth analyzers.

After analyzing the data and running follow-up experiments — it can design and initiate over a thousand new experiments each day — Adam had uncovered three genes that together coded for an orphan enzyme. King’s group confirmed the novel findings by hand.

Waltz thinks Adam will inspire other scientists. “They will realize they can automate more of the process than they currently have. They can explore a wider range of possibilities without doing it all by hand.”

King is already expanding his Robot Scientist fleet by producing Eve, which will autonomously design and screen drugs against malaria and schistosomiasis.

“Most drug discovery is already automated,” says King, “but there is no intelligence — just brute force.” King says Eve will use artificial intelligence to select which compounds to run, rather than just following a list.

If robotic scientists made their way into other labs, their human counterparts would not be out of a job anytime soon. If anything, they may find their work more exciting.
“There may be teams of humans and machines,” says King.

“Robots will be doing more and more of actual experimental work and simple cycles of hypothesis generation. Humans would migrate to more strategic and creative positions. How can we waste trained post-docs by making them pipette things in labs? It’s crazy.”

But with advances in artificial intelligence, it is conceivable that the role of robots would, in the more distant future, creep deeper into the human realm, progressing from lab technician to lab head.

Robots may even be capable of performing supposed acts of genius, such as Einstein’s conception of special relativity.

“There is not any intrinsic reason why that would not happen,” says King. “I think there is a continuum between the really basic types of science that you would get from Adam, and the things I can do, and then Einstein-type science. A computer can make beautiful chess moves, but it is not doing anything special. It is just doing more of the same thing. In my view that is what is going to happen in science.”

King may already have a head start: Deep Blue could never have beaten Garry Kasparov without engineer Feng-Hsiung Hsu moving the pieces on its behalf.

(http://blog.wired.com/wiredscience/2009/04/robotscientist.html)

Critics Object to ‘Pseudoscience’ Center

From the FMS Global News Desk of Jeanne Hambleton
Courtesy of washingtonpost.com – Health

By David Brown – Washington Post Staff Writer
Tuesday, March 17, 2009; Page HE01

The impending national discussion about broadening access to health care, improving medical practice and saving money is giving a group of scientists an opening to make a once-unthinkable proposal: Shut down the National Center for Complementary and Alternative Medicine at the National Institutes of Health.

The notion that the world’s best-known medical research agency sponsors studies of homeopathy, acupuncture, therapeutic touch and herbal medicine has always rankled many scientists. That the idea for its creation 17 years ago came from a U.S. senator newly converted to alternative medicine’s promise did not help.

Although NCCAM has a comparatively minuscule budget and although it is a “center” rather than an “institute,” making it officially second-class in the NIH pantheon, the principle is what mattered. But as NIH’s budget has flattened in recent years, better use for NCCAM’s money has also become an issue.

“With a new administration and President Obama’s stated goal of moving science to the forefront, now is the time for scientists to start speaking up about issues that concern us,” Steven Salzberg, a genome researcher and computational biologist at the University of Maryland, said last week. “One of our concerns is that NIH is funding pseudoscience.”

Salzberg suggested that NCCAM be defunded on an electronic bulletin board that the Obama transition team set up to solicit ideas after November’s election. The proposal generated 218 comments, most of them in favor, before the bulletin board closed on Jan. 19.

NCCAM has grown steadily since its founding in 1992, largely at the insistence of Sen. Tom Harkin (D-Iowa), as the Office of Alternative Medicine (OAM) with a budget of $2 million. In 1998, NIH director and Nobel laureate Harold Varmus pushed to have all alternative medicine research done through NIH’s roughly two dozen institutes, with OAM coordinating, and in some cases paying for, the studies. Harkin parried with legislation that turned OAM into a higher-status “center” (although not a full-fledged “institute”), and boosted its budget from $20 million to $50 million. NCCAM’s budget this year is about $122 million.

Research in alternative medicine is done elsewhere at NIH, notably in the National Cancer Institute, whose Office of Cancer Complementary and Alternative Medicine also has a budget of $122 million.

The entire NIH alternative medicine portfolio is about $300 million a year, out of a total budget of about $29 billion. (NIH will get an additional $10.4 billion in economic stimulus money over the next two years, of which $31 million is expected to go to NCCAM.)

Critics of alternative medicine say the vast majority of studies of homeopathy, acupuncture, therapeutic touch and other treatments based on unconventional understandings of physiology and disease have shown little or no effect. Further, they argue that the field’s more-plausible interventions — such as diet, relaxation, yoga and botanical remedies — can be studied just as well in other parts of NIH, where they would need to compete head-to-head with conventional research projects.

The critics say that alternative medicine (also known as “complementary” and “integrative” medicine, and disparagingly labeled “woo” by opponents) does not need or deserve its own home at NIH.

“What has happened is that the very fact NIH is supporting a study is used to market alternative medicine,” said Steven Novella, a neurologist at Yale School of Medicine and editor of the Web site Science-Based Medicine (http://www.sciencebasedmedicine.org), where much of the anti-NCCAM discussion is taking place. “It is used to lend an appearance of legitimacy to treatments that are not legitimate.”

Beyond the Blogosphere

So far, most of the debate has occurred in the blogosphere. But as health-care reform moves toward center stage, so may this fight.

At a Senate committee hearing on integrative medicine held Feb. 26, Harkin said: “I want to lay down a . . . marker: If we fail to seize this unique opportunity to adopt a pragmatic, integrative approach to health care, then that, too, would constitute a serious failure.”

At the hearing, Harkin introduced Berkley W. Bedell, a six-term Democratic congressman from Iowa who retired in 1987 after contracting Lyme disease. Bedell credits alternative therapies for his recovery from that infection and later from prostate cancer. He helped convince the Iowa senator of alternative medicine’s promise.

Nevertheless, Harkin said he was somewhat disappointed in NCCAM’s work.

“One of the purposes when we drafted that legislation in 1992 . . . was to investigate and validate alternative approaches. Quite frankly, I must say it’s fallen short,” he told the committee.

“I think quite frankly that in this center, and previously in the office before it, most of its focus has been on disproving things, rather than seeking out and proving things.”

Critics say this shows Harkin’s lack of understanding of scientific inquiry, which tests hypotheses (with negative results as informative as positive ones) but doesn’t intentionally attempt to “validate approaches.” NCCAM’s current director, Josephine P. Briggs, agrees that hypothesis-testing is the proper function of the center.

“We are not advocates for these modalities,” she said last week. “We are trying to bring rigor to their study and make sure the science is objective.”

Even so, Harkin was on to something: Most of NCCAM’s results have been negative or inconclusive, not positive and encouraging.

For example, a randomized controlled trial of the botanical echinacea published in 2003 found it was ineffective in treating upper respiratory infections (although it did cause more rashes). In a study from last year, neither the Japanese “palm healing” therapy known as reiki, nor sham reiki, reduced the symptoms of fibromyalgia, a chronic pain syndrome. A study in December comparing real and sham acupuncture in 162 cancer patients who’d undergone surgery found no difference in their levels of pain.

At the same time, it’s difficult to determine the clinical implications of some of the positive studies.

For example, reiki — but not sham treatment — blunted the rise in heart rate, but not the rise in blood pressure, in rats put under stress by loud noise. Therapeutic touch, a different modality, increased the growth of normal bone cells in culture dishes, but decreased the growth of bone cancer cells.

Many NCCAM-funded studies examine not the effectiveness of alternative medicine but its use, and how it affects the interaction of practitioners and patients. The idea that the center is spending lots of money running large clinical trials of such practices as homeopathy and ayurvedic medicine “is a misperception,” the director said. She noted that most such proposals lack methodological rigor and are not approved.

A physician and kidney specialist who never used alternative medicine in her practice, Briggs said “mind-body management for pain control and stress reduction” is a large topic of the research at the moment, with mindfulness, meditation, yoga and tai chi all under study.

“Some of the way these approaches work is through ‘positive expectancy,’ which is part of a placebo effect,” she said.

Indeed, many of NCCAM’s critics view complementary medicine as nothing more than the placebo effect dressed up in a dozen different costumes.

Carlo Calabrese, a researcher at the National College of Natural Medicine in Portland, Ore., one of the country’s five naturopathic medical schools, is not one of them. But even if one were to concede that view, he thinks the field is still worth studying.

Although the overall effect of therapies such as homeopathy and acupuncture may be small, individual response can be large. The route to the placebo effect — if that’s what it mostly is — also varies in method and efficiency.

“What can be done to generate a better placebo? Why isn’t that an interesting and valid area of investigation?” said Calabrese, who was on NCCAM’s advisory council from 2004 to 2007. “Here we have a totally harmless intervention that seems to get a better result in some people than others. Why wouldn’t you want to study that?”

Comments: browndm@washpost.com.

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What Makes a Disease Real?

From the FMS Global News Desk of Jeanne Hambleton

Contents provided by the Harvard Medicine School – Courtesy MSN.health&fitness

Some conditions cannot be diagnosed with any test
By Robert Shmerling, M.D., Harvard Health Publications

Doctors can be a skeptical bunch. I have colleagues who flat out deny that a condition can be “real” unless they can observe it or detect it with a test.

Yet, many physicians deal with conditions all the time whose symptoms can’t be measured. For example:

Depression—A depressed person will usually have normal physical examinations, blood tests and, if necessary, a normal brain MRI.
Headaches—Most people who have headaches have normal test results.
Joint pain—People can have joint pain (arthralgia) without any joint inflammation (arthritis). The pain could be due to tendonitis, bursitis, vitamin D deficiency or thyroid disease. But often we can’t find any cause of the pain.

Doctors rarely do extensive testing for these conditions because abnormal results are rare and the tests are almost never helpful.

Millions of people are affected by diseases that have “subjective” symptoms and cannot be confirmed by observation or tests. These include fibromyalgia, most headaches (including migraine), irritable bowel syndrome. So, does this mean that these conditions aren’t “real?” They’re certainly real to the people suffering with them.

“It is all in your head”.

When a symptom cannot be explained, it does not mean that it is imaginary or due to a mental illness, psychiatric disorder or psychological distress. That is what is implied when a doctor tells a patient, “It’s all in your head.” At the very least, we should assume that the pain or unpleasant experience is real regardless of test results.

In the end, all pain is perceived by the brain. So, in a way, all pain is “all in your head.” Yet there is a tendency to relegate unobservable symptoms to the realm of the psychiatrist. Never mind that a psychiatric disease is “real” even when imaging and blood test results are normal. If you have ever witnessed psychotic behavior or been with someone who is severely depressed, it is clearly real.

Unexplained symptoms could be due to a disease that has not been detected yet. Ideally, doctors and patients should identify the cause if possible, rule out a dangerous condition, and treat the bothersome symptoms. And that is true whether the symptom is measureable or not.

What is in a name?

We usually expect the doctor to make a diagnosis and recommend a treatment when we have a problem. It is reassuring to know that your particular problem has a name. It means that other people have experienced it and that studies have assessed the effectiveness of various treatments.

Yet for many conditions, the name is only a label. It is convenient to apply a name to a particular combination of symptoms, even though the cause is unknown and no clear-cut abnormalities can be found. Examples include fibromyalgia syndrome and irritable bowel syndrome. Assigning a name to symptoms can be reassuring but it does not make the condition more or less “real.”

Focus on improving symptoms

There are times when even the smartest health care provider cannot come up with a logical, compelling or even reasonable explanation for a person’s symptoms. In those cases, it is important not to get too focused on explaining or labeling them. Instead, the doctor should focus on:

Not missing some important clue

Treating the symptoms

In many fields of medicine, doctors spend all day improving symptoms rather than making a diagnosis. Headache specialists, for example, must be convinced there is no brain tumor, no meningitis, and no other serious and treatable cause of the pain. But once that happens, attention turns toward treatment rather than on sorting out a specific cause.

This can be frustrating for both patients and doctors. But until we understand the specific causes of common conditions like headaches, back pain, ringing in the ears (tinnitus) and chronic fatigue, controlling symptoms, not a name, is what will help the most.

The bottom line

Once again this shows that there is more uncertainty in medicine than most people think. But that does not mean a person is imagining their symptoms.

As I see it, debating the “realness” of symptoms is often a waste of time. Unless a person is deliberately “faking” symptoms (a rare event in most doctors’ practices), they are just as real as for those with an observable, measurable and testable condition.

Having names are nice, but they are not always helpful. All other things being equal, I would rather have a nameless condition that is well-treated than a definite, but untreatable diagnosis.

Copyright © 2009 by the Presidents and Fellows of Harvard College. Used with permission of StayWell. All rights reserved. Harvard Medical School does not approve or endorse any products on the page. Harvard is the sole creator of its editorial content, and advertisers are not allowed to influence the language or images Harvard uses.

(http://health.msn.com/health-topics/articlepage.aspx?cp-documentid=100233740)

Health Benefits of Intravenous Nutrient Therapy – Myers Cocktail

From the FMS Global News Desk of Jeanne Hambleton

Courtesy HealthNotesNewswire

By Darin Ingels, ND

EDITOR’S NOTE: While I appreciate this was written in 2003 I do know that many fibromites are regularly given the ‘Myers Cocktail’ to relieve pain. I felt the background would be interesting. However I would recommend you read the Consumer Alert written May/June 2007 on the FM Net News website (http://www.fmnetnews.com/resources-alert-product8.php) for another view point. Please do not shoot the messenger I am merely reporting what I have found. I have a good friend who has these injections from time to time and she believes they do her the world of good. See the FM Net News report. Without prejudice. JH)

Healthnotes Newswire (January 16, 2003)

Administering a vitamin and mineral formula (known as the Myers cocktail?) intravenously may be useful in treating a variety of medical problems, according to a report in Alternative Medicine Review (2002;7:389?403). Although few studies have been published on this therapy, many physicians have observed its benefit in treating migraine headaches, fatigue, allergies, heart disease, acute asthma attacks, fibromyalgia, infections, and other conditions.

The Myers cocktail was pioneered by John Myers, MD, a physician from Baltimore, Maryland, who developed this treatment more than 30 years ago. The doses of the various nutrients were subsequently modified, based on more recent information, by Alan R. Gaby, MD, the author of the report.

The vitamin-mineral combination includes magnesium, calcium, vitamin B12 (hydroxocobalamin), vitamin B6 (pyridoxine), vitamin B5 (dexpanthenol), vitamin B complex, and vitamin C. Intravenous therapy can raise blood levels of nutrients to a considerably greater extent than oral therapy can, and some doctors believe that achieving these high blood levels has therapeutic benefits in certain clinical situations. The benefits of the Myers cocktail may be due to the drug-like (pharmacological) effects of some nutrients (for example, high concentrations of vitamin C kills viruses), or to improved transport of nutrients from the blood into the cells. More research is necessary to clarify this issue.

Some physicians who use the Myers cocktail report that it is particularly useful in treating acute asthma attacks and acute migraine headaches. Relief of symptoms usually occurs within minutes of administering the concoction. It is not clear whether the benefits are due to one nutrient or to the combination of nutrients, but other studies have shown that intravenous magnesium alone can reduce the symptoms of asthma and migraines. However, the author?s observation is that the Myers cocktail is more beneficial for acute asthma attacks than is magnesium alone.

The author and other physicians have found that the Myers cocktail is also useful in treating angina, chronic fatigue syndrome, bronchitis, sinusitis, fibromyalgia, hayfever, chronic hives, narcotic withdrawal, hyperthyroidism, muscles spasms, tension headaches, and some cases of mild to moderate depression. While many people improved after the first treatment, others required several treatments to achieve the maximum benefit, suggesting this therapy may have a cumulative effect. The number of treatments needed varies by person and condition. Some individuals obtain long-lasting relief after a few treatments, while others require ongoing treatments to maintain the benefit. The risk of serious adverse reactions is said to be low and the treatment is usually well tolerated.

The most common side effect of the Myers cocktail is a sensation of warmth, particularly if the injection is given rapidly. This effect is primarily due to magnesium, although calcium may also be a contributing factor. People with low blood pressure may be more prone to this side effect than those with normal or high blood pressure. People taking digoxin (Lanoxin®) and medications that deplete potassium should be cautious in using this treatment, since giving magnesium intravenously to such individuals could induce an irregular heart beat. The Myers cocktail can be prescribed only by a medical doctor, osteopath, or, in some states, a naturopath.

Although most of the reported benefits of the Myers cocktail are anecdotal, doctors who use this treatment are convinced that it often produces results not achievable by any other means. Controlled studies are needed to verify these clinical observations.

Darin Ingels, ND, MT (ASCP), received his bachelor?s degree from Purdue University and his Doctorate of Naturopathic Medicine from Bastyr University in Kenmore, WA. Dr. Ingels is the author of The Natural Pharmacist: Lowering Cholesterol (Prima, 1999) and Natural Treatments for High Cholesterol (Prima, 2000). He currently is in private practice at New England Family Health Associates located in Southport, CT, where he specializes in environmental medicine and allergies. Dr. Ingels is a regular contributor to Healthnotes and Healthnotes Newswire.

Copyright © 2003 Healthnotes, Inc. All rights reserved. Healthnotes Newswire is for educational or informational purposes only, and is not intended to diagnose or provide treatment for any condition. If you have any concerns about your own health, you should always consult with a healthcare professional. Healthnotes, Inc. shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Healthnotes and the Healthnotes logo are registered trademarks of Healthnotes, Inc.

(http://www.thevitaminservice.com:healthnotes.asp%3Forg=vitaminservice&page=newswire:newswire_2003_01_16_2.cfm..webarchive)

Consumer Alerts Myers’ Cocktail
Courtesy Fibromyalgia Network

Many treatment centers for fibromyalgia are heavily promoting the use of intravenous (IV) Myers’ nutrient therapy, or what many call a modified Myers’ cocktail. The advertisements often boast that you can receive up to 60% reduction in pain and an 80% reduction in fatigue. They also claim that you will notice these symptom improvements within two days of receiving the Myers’ IV cocktail.

Myers was a physician who believed that an IV infusion of the ingredients below would help jump-start symptom improvements (especially fatigue) in people with chronic illnesses, but never published data to substantiate his theory. So why is it that treatment centers are claiming you can reap amazing improvements in pain and fatigue with the Myers’ cocktail? They are basing it on a report of seven women with fibromyalgia (and no control subjects for comparison) by Patrick Massey, M.D., Ph.D., of Elk Grove Village, IL.*

Although Massey is to be commended for trying to evaluate a nutrient treatment for fibromyalgia patients, the results of his study are being taken out of context for the promotional use of this expensive therapy ($200 – $300 a shot). Massey selected seven fibromyalgia patients who were already under his care and tried to help them with eight weekly Myers’-type IV infusions. He asked the seven patients to rate their pain and fatigue prior to the first IV, and then to rate these symptoms as a weekly average when they returned to his office for the next infusion. The seven patients knew that they were being given something new to help ease their fibromyalgia symptoms, which could understandably lead to high expectations for health improvements. This was not a blinded or placebo-controlled study.

Massey states in his report that the eight-week therapy reduced pain by 60% and fatigue by 80%. However, due to the lack of a placebo comparison group, the small number of patients in the study, the power of suggestion (the “white coat” effect because doctors often wear white lab coats), and the fact that all seven patients knew they were receiving the nutrient therapy and not a placebo, patients cannot bank on these results. The mere power of suggestion by the person in the white coat (even if it is not intended) may produce phenomenal results from a placebo or sugar pill.

In the discussion part of the report, Massey comments that the therapy is short-lived-lasting between 24 and 48 hours. Yet he provides no data to substantiate this claim. Promoters of the IV Myers’ cocktail may reference the 24-48 hour time frame to imply the speed at which patients should notice symptom improvements, but it is actually the estimated duration of the relief. If you have received IV nutrient therapies before, only to find that they do not produce long-lasting symptom benefits (if any at all), this could be the reason why. Yet, regular infusions of this nature are not practical and they are expensive (approximately $250 per infusion).

Why is the Myers’ cocktail so expensive? Any treatment approach that includes an IV is costly. The ingredients in this IV therapy are relatively cheap when taken orally as nutritional supplements. If one were to take the nutrients in the IV dose over 48 hours as an oral supplement, then the cost per month would be less than $15, as compared to four IV treatments a month totaling about $1,000. (See the third column in the table above for the daily equivalent oral doses.) Patients who are concerned that their diet is deficient in these essential nutrients have little to lose by trying this oral supplementation approach. All you need to do is purchase three supplements: 1) vitamin B complex, 2) vitamin C, and 3) magnesium. The vitamin C formula should be buffered and the magnesium should be chelated so these supplements are gentle on your stomach.

* Massey PB. Alternative Therapies 13(3):32-34, May/June 2007.

Modified Myers’ IV Formula (may provide up to 48 hours of relief) includes the following:
Magnesium chloride hexahydrate, Calcium gluconate, Vitamin C , Hydroxocobalmin (B12) , Pyridoxine hydrochloride (B6), Dexpanthenol (B5) Riboflavin (B2), Thiamine (B1), Niacinamide (B3).
Estimated Costs $250/IV Dose, $15/Month. For quantities please log on to the Fibromyalgia Network website as below.

(http://www.fmnetnews.com/resources-alert-product8.php)

All information on this site is copyrighted by Fibromyalgia Network, P.O. Box 31750, Tucson, AZ 85751 (800) 853-2929.
This site is provided for informational purposes only. To remain unbiased, we do not accept endorsements, advertisements, or pharmaceutical industry grants. Patients should always consult their physician for medical advice and treatment.

Chili Pepper Compound Can Bring Pain Relief

From the FMS News Desk of Jeanne Hambleton

COURTESY usnews.com Health Day – Monday March 16

Capsaicin works on nerves to ease joint discomfort, scientists say

(HealthDay News) – University of Buffalo scientists say they have found how capsaicin, the compound that gives chili peppers their fiery flavor, also works to relieve joint and muscle pain.

In a study appearing Tuesday in the journal PLoS Biology, researchers found that capsaicin flips on nerve-ending receptors that sense both pain and heat.

“The receptor acts like a gate to the neurons. When stimulated it opens, letting outside calcium enter the cells until the receptor shuts down, a process called desensitization,” study leader Feng Qin, an associate professor at the university’s School of Medicine and Biomedical Sciences, said in a news release issued by the institution.
The flood of calcium changes the levels at which the receptors detect pain signal. “In other words, the receptor had not desensitized per se, but its responsiveness range was shifted,” Qin said.

While capsaicin has been used in folk medicines for generations, knowing how it works in relation to PIP2 may lead to developing other analgesics that ease pain without first causing irritation on their own, the team said.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more about capsaicin .
(http://health.usnews.com/articles/health/healthday/2009/02/25/chili-pepper-compound-can-bring-pain-relief.html)

Finding Effective Treatment for Your Chronic Pain

Studies are underway to look into the effectiveness of alternative ways of delivering pain medications

By January W. Payne

Chronic pain is a problem that—when healthcare, lost income, and lost productivity are taken into account—is estimated to cost about $100 billion in the United States each year. More than a quarter of Americans age 20 or older, or about 76.5 million people, say they’ve experienced pain that lasted longer than 24 hours, according to the American Pain Foundation—and 42 percent have endured pain lasting longer than a year. Nobody keeps good long-term national stats, but if North Carolina’s experience is any guide, the numbers are on the rise.

A just-published study in the Archives of Internal Medicine found that the prevalence of chronic low-back pain in the state more than doubled, to 10.2 percent, between 1992 and 2006. Paul J. Christo, assistant professor and director of the Multidisciplinary Pain Fellowship at the Johns Hopkins University School of Medicine, calls undiagnosed, untreated, or undertreated pain a “significant public-health problem.”

Chronic pain encompasses a multitude of ills, from back pain, headaches, neck pain, and conditions like arthritis and fibromyalgia to pain that develops as a result of cancer treatment and lingers for months or even years. Low-back pain, migraines, and joint pain (particularly in the knees) are among the most common complaints, according to the National Center for Health Statistics. knee pains,

Still, while it may have different origins, chronic pain “can be viewed as an illness in its own right because of its effect on function,” says Russell Portenoy, chairman of the department of pain medicine and palliative care at Beth Israel Medical Center in New York City.

Studies have shown that some people with chronic pain have brain abnormalities, though the connection between that and pain is not well understood. One recent study, for instance, showed that women with fibromyalgia had blood flow abnormalities in a region of the brain known to discriminate the intensity of pain that were not observed on CT scans done in healthy women.

Another study showed that chronic pain may harm the wiring of the brain, as demonstrated on functional MRIs. Chronic pain may also be caused by a problem with the “fight or flight” response, Christo says. “We believe that in certain pain conditions . . . the stress response can worsen pain because that stress response releases a chemical called noroepinephrine. . . . And noroepinephrine binds to certain receptors in the body that trigger pain.”

“Pain is essentially an alarm system that is designed to grab your attention, and when it works properly, it signals harm or healing,” says Scott Fishman, professor and chief of the division of pain medicine at the University of California-Davis School of Medicine. When the body heals, the pain should dissipate, but “the nervous system can become injured,” Fishman says. “That’s when the symptom of pain becomes the disease of chronic pain.”

Finding relief can take quite an effort, since the causes are often not immediately clear and there is not a sure-fire treatment. The battle can require a team of experts, so the multidisciplinary pain clinics or pain management programs that have sprouted up at hospitals, rehab centers, and in free-standing facilities over the past decade or so may be of particular help.

The clinics provide an all-in-one setting for care that, in addition to pain management specialists who may be trained as neurologists, psychiatrists, physiatrists, or anesthesiologists, may include physical therapists, family and vocational counselors, and massage therapists, for example. (The American Chronic Pain Association offers advice on selecting a pain clinic.)

After a full assessment, tailored treatment may include medications from anti-inflammatory drugs to antidepressants to opioids. Since commonly prescribed opioid medications such as oxycodone, fentanyl, and morphine can cause addiction, the American Pain Society and the American Academy of Pain Medicine have just released the first comprehensive clinical practice guidelines to help physicians make treatment decisions.

The guidelines, published in the Journal of Pain, suggest that physicians regularly assess people taking long-term opioids and do periodic drug screenings of patients who are considered to be at risk for abuse or addiction. Meanwhile, the Food and Drug Administration announced plans this month to require the brand-name and generic makers of morphine, oxycodone, fentanyl, and methadone to assist with a plan to reduce the risks associated with the drugs.

Other treatment options include injections of steroids or other medications, nerve blocks that interrupt pain signals, physical therapy, alternative therapies, and psychological interventions such as cognitive behavioral therapy, biofeedback, and guided imagery and other relaxation techniques. Acupuncture, which some people with pain find helpful, is thought to ease pain by raising the level of endorphins in the body, Christo says. “Endorphins are sort of like opioids. . . . They are natural pain relievers,” he says.

“They are released when the body experiences pain—when you sprain your ankle, cut your finger, in response to injury.” Still, research offers conflicting conclusions about the pain-relieving effects of acupuncture. A review of 13 studies published last month in British Medical Journal found that acupuncture offered only a small level of pain relief for people with low-back pain, migraines, knee osteoarthritis, and postoperative pain.

Jennifer Phillips, 41, of Providence Forge, Va., saw 54 doctors before the fibromyalgia that caused her pain was diagnosed in 1996. Finally, after seeing an internist whose nurse had fibromyalgia, she found a routine that works for her: a combination of proper sleep (achieved, in part, using the tricylic antidepressant amitriptyline), daily supplements of vitamins, magnesium, and potassium, plenty of water, and a low-carb diet.

The search is on for greater relief. Studies are underway to look into the safety and effectiveness of alternative ways of delivering pain medications, such as an inhaled form of fentanyl that would get the drug into the patient’s system more quickly. For older people who have fractures of the spine, vertebroplasty and kyphotlasty—two minimally invasive techniques in which bone cement is injected into the collapsed bone in the spine—can result in “significant pain reduction,”

Christo says. In the ongoing debate over how best to handle back pain, a study just published in the Journal of the American Academy of Orthopaedic Surgeons finds that the most effective way to treat most degenerative disc disease cases is to combine physical therapy and anti-inflammatory medications, rather than having surgery.
While it may seem counterintuitive, people with chronic pain should try to get exercise. Experts say it is important to keep moving, both for the usual cardiovascular reasons and in order to avoid muscle atrophy. A supervised, individually designed exercise program, incorporating stretching or strengthening, may improve pain and functioning in people with chronic low-back pain, according to a 2005 study published in Annals of Internal Medicine.

A physical therapist or personal trainer can offer the necessary advice. In fact, staying in bed for more than a day or two can make back pain worse, according to the National Library of Medicine’s MedlinePlus.

Jeff Nance of Indianapolis, whose chronic pain is caused by degenerative disc disease and spinal stenosis of his lower back, recalls that he barely wanted to leave his home three years ago. Then he discovered the Meridian Health Group pain clinic in Indianapolis. Now he is working full time again, and he recently participated in an annual bike ride across the state of Indiana. Nance goes back to the clinic every few months for a check of his medications, and he sees a psychologist a couple of times a month.

“What we try to do is really recognize that people can have pain for all kinds of reasons, [and we] find as many of those causes as possible and treat them in the most specific fashion as possible,” says Michael Clark, associate professor and director of the Chronic Pain Treatment Program in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins Hospital. “Ultimately, you’d like to get somebody well.”

(http://health.usnews.com/articles/health/pain/2009/02/10//finding-effective-treatment-for-your-chronic-pain.html?loomia_ow=t0:a41:g2:r2:c0.160667:b22273524&s_cid=loomia:chili-pepper-compound)

Copyright © 2009 U.S.News & World Report LP All rights reserved.

EINSTEIN RESEARCHERS DEVELOP NOVEL ANTIBIOTICS THAT DON’T TRIGGER RESISTANCE

From the FMS Global News Desk of Jeanne Hambleton

Courtesy Einstein News – Albert Einstein College of Medicine

March 12, 2009 — (BRONX, NY) — Bacterial resistance to antibiotics is one of medicine’s most vexing challenges. In a study described in Nature Chemical Biology, researchers from Albert Einstein College of Medicine of Yeshiva University are developing a new generation of antibiotic compounds that do not provoke bacterial resistance. The compounds work against two notorious microbes: Vibrio cholerae, which causes cholera; and E. coli 0157:H7, the food contaminant that each year in the U.S. causes approximately 110,000 illnesses and 50 deaths.

Vern Schramm, Ph.D.Most antibiotics initially work extremely well, killing more than 99.9% of microbes they target. But through mutation and the selection pressure exerted by the antibiotic, a few bacterial cells inevitably manage to survive, repopulate the bacterial community, and flourish as antibiotic-resistant strains.

Vern L. Schramm, Ph.D., professor and Ruth Merns Chair of Biochemistry at Einstein and senior author of the paper, hypothesized that antibiotics that could reduce the infective functions of bacteria, but not kill them, would minimize the risk that resistance would later develop.

Dr. Schramm’s collaborators at Industrial Research Ltd. earlier reported transition state analogues of an enzyme that interferes with “quorum sensing” — the process by which bacteria communicate with each other by producing and detecting signaling molecules known as autoinducers. These autoinducers coordinate bacterial gene expression and regulate processes — including virulence — that benefit the microbial community. Previous studies had shown that bacterial strains defective in quorum sensing cause less-serious infections.
Rather than killing Vibrio cholerae and E. coli 0157:H7, the researchers aimed to disrupt their ability to communicate via quorum sensing. Their target: A bacterial enzyme, MTAN, that is directly involved in synthesizing the autoinducers crucial to quorum sensing. Their plan: Design a substrate to which MTAN would bind much more tightly than to its natural substrate — so tightly, in fact, that the substrate analog permanently “locks up” MTAN and inhibits it from fueling quorum sensing.

To design such a compound, the Schramm lab first formed a picture of an enzyme’s transition state — the brief (one-tenth of one-trillionth of a second) period in which a substrate is converted to a different chemical at an enzyme’s catalytic site. (Dr. Schramm has pioneered efforts to synthesize transition state analogs that lock up enzymes of interest. One of these compounds, Forodesine, blocks an enzyme that triggers T-cell malignancies and is currently in a phase IIb pivitol clinical study treating cutaneous T-cell leukemia.)

Biofilm formation in pathogenic Vibrio cholerae N16961 cell culture is inhibited by MTAN inhibitor butylthio-DADMe-ImmucillinA
(BuT-DADMe-ImmA), biofilm (indicated by white arrows) is visibly reduced in the presence of 1 micromolar inhibitor.In the Nature Chemical Biology study, Dr. Schramm and his colleagues tested three transition state analogs against the quorum sensing pathway. All three compounds were highly potent in disrupting quorum sensing in both V. cholerae and E. coli 0157:H7. To see whether the microbes would develop resistance, the researchers tested the analogs on 26 successive generations of both bacterial species. The 26th generations were as sensitive to the antibiotics as the first.

“In our lab, we call these agents everlasting antibiotics,” said Dr. Schramm. He notes that many other aggressive bacterial pathogens — S. pneumoniae, N. meningitides, Klebsiella pneumoniae, and Staphylococcus aureus — express MTAN and therefore would probably also be susceptible to these inhibitors.

While this study involves three compounds, Dr. Schramm says that his team has now developed more than 20 potent MTAN inhibitors, all of which are expected to be safe for human use: Since MTAN is a bacterial enzyme, blocking it will have no effect on human metabolism.
Other Einstein researchers involved in the study were Jemy Gutierrez, the lead author, Tamara Crowder, Agnes Rinaldo-Matthis, M. C. (Joseph) Ho and Steven C. Almo. The powerful inhibitors were reported in an earlier publication in collaboration with the Carbohydrate Chemistry Team of Industrial Research Ltd., in New Zealand.

The study, “Transition State Analogs of 5′ — Methylthioadenosine Nucleosidase Disrupt Quorum Sensing” by Vern L. Schramm et al., appears in the March 8, 2009 online edition of Nature Chemical Biology.

The compounds in this paper have been licensed to Pico Pharmaceuticals, which plans to develop and initiate clinical trials of transition-state analogues. Dr. Schramm is a Pico Pharmaceuticals co-founder and chairman of its scientific advisory board.

(http://www.aecom.yu.edu/home/news.asp?id=317)