Health Technology Research Synopsis
32nd Issue Date 11 JUN 2008
Compiled By Ralph Turchiano
Editors Top Five:1. US reporters often do a poor job of reporting about new medical treatments
2. Pycnogenol improved diabetes control and reduced antihypertensive medications
3. How advanced prostate cancer becomes resistant to androgen-deprivation therapy
4. Is tap water safe for expectant mothers?
5. The good news in our DNA: Defects you can fix with vitamins and minerals
In this issue:
1. Childhood lead exposure associated with criminal behavior in adulthood
2. US reporters often do a poor job of reporting about new medical treatments
3. People with ADHD do 1 month’s less work per year
4. Combining exercise with hormone could prevent weight gain
5. Estrogen Helps Drive Distinct, Aggressive Form of Prostate Cancer
6. New breathing exercises help manage asthma
7. Intestinal bacteria promote — and prevent — inflammatory bowel disease
8. New vegetarian food with several benefits
9. Pycnogenol improved diabetes control and reduced antihypertensive medications
10. Dehydrated tomatoes show promise for preventing prostate cancer
Exercise cuts cancer death in men
12. US soldiers in high-tuberculosis areas face new epidemic: false positives
13. Whole milk is effective and cost-effective as oral contrast agent
14. How advanced prostate cancer becomes resistant to androgen-deprivation therapy
15. Bisphenol A: Controversy over widely used plastics chemical spurs product changes, regulatory debate
16. Vitamins Help Prevent Vision Loss from AMD—If Used Correctly
17. The good news in our DNA: Defects you can fix with vitamins and minerals
18. Is tap water safe for expectant mothers?
19. Despite vaccine, public should not get complacent about pneumococcal disease
20. Agent in red wine found to keep hearts young
21. Increased Incidence of Melanoma Found in Rheumatoid Arthritis Patients Treated with Methotrexate
22. Long-term pesticide exposure may increase risk of diabetes
23. Moores UCSD Cancer Center study links vitamin D, type 1 diabetes
24. Another new wrinkle in treating skin aging
25. Study finds Chinese food good for your heart
26. Men with vitamin D deficiency may have increased risk of heart attack
27. Eating fish and foods with omega-3 fatty acids linked to lower risk of age-related eye disease
28. World’s oldest woman had normal brain
29. Solid tumor cells not killed by radiation and chemotherapy become stronger
30. Common bowel problem linked to chili pepper pain receptor
Public release date: 27-May-2008
Childhood lead exposure associated with criminal behavior in adulthood
CINCINNATI—New research from the University of Cincinnati (UC) reports the first evidence of a direct link between prenatal and early-childhood lead exposure an increased risk for criminal behavior later in life.
Based on long-term data from a childhood lead study in Cincinnati, Ohio, Kim Dietrich, PhD, and his team have determined that elevated prenatal and postnatal blood-lead concentrations are associated with higher rates of criminal arrest in adulthood.
“Previous studies either relied on indirect measures of exposure or failed to follow subjects into adulthood to examine the relationship between lead exposure and criminal activity in young adults,” explains Dietrich, principal investigator of the study and professor of environmental health at UC.
“We have monitored this specific sub-segment of children who were exposed to lead both in the womb and as young children for nearly 30 years,” he adds. “We have a complete record of the neurological, behavioral and developmental patterns to draw a clear association between early-life exposure to lead and adult criminal activity.”
Dietrich says few studies have attempted to evaluate the consequences of childhood lead exposure as a risk of criminal behavior. The UC-led study is the first of its kind to demonstrate an association between developmental exposure to lead and adult criminal behavior.
Dietrich and his colleagues report their findings in the May 27, 2008, issue of the journal PLoS Medicine.
This new study is part of a long-term lead exposure study conducted through the Cincinnati Children’s Environmental Health Center, a collaborative research group funded by the National Institute of Environmental Health Sciences (NIEHS) and U.S. Environmental Protection Agency (EPA) that involved scientists from the UC College of Medicine and Cincinnati Children’s Hospital Medical Center.
Led by Dietrich, researchers recruited pregnant women living in Cincinnati neighborhoods with a higher concentration of older, lead-contaminated housing. Recruitment took place at four prenatal clinics between 1979 and 1984. Dietrich’s team has monitored this population group since birth to assess the long-term health effects of early-life lead exposure.
Of the original 376 newborns recruited, 250 were identified for the current study. Researchers measured blood-lead levels during pregnancy and then at regular intervals until the children were 6 ½ years old to calculate cumulative lead exposure.
Blood-lead level data was then correlated with public criminal arrest records from a search of Hamilton County, Ohio, criminal justice records. These records provided information about the nature and extent of arrests and were coded by category: violent, property, drugs, fraud, obstruction of justice, serious motor vehicle, disorderly conduct and other offenses.
Researchers found that individuals with increased blood-lead levels before birth and during early childhood had higher rates of arrest—for both violent and total crimes—than the rest of the study population after age 18.
Approximately 55 percent of the subjects had at least one arrest—the majority of which involved drugs (28 percent) or serious motor vehicle violations (27 percent). The strongest association between childhood blood-lead level and criminal behavior was for arrests involving acts of violence.
Dietrich says that although both environmental lead levels and crime rates in the United States have dropped in the past 30 years, they have not done so in a uniform way.
“Lower income, inner-city children remain particularly vulnerable to lead exposure,” he explains. “Although we’ve made great strides in reducing lead exposure, our findings send a clear message that further reduction of childhood lead exposure may be an important and achievable way to reduce violent crime.
“Aggressive or violent behavioral patterns often emerge early and continue throughout life,” adds Dietrich. “Identifying the risk factors that may place youth on an early trajectory toward a life of crime and violence should be a public health priority.”
Study coauthor John Wright, PhD, a member of UC’s criminal justice faculty who studies the impact of factors like genetics, psychology and biology on criminality, says he had limited expectations for how strong a correlation between lead exposure and criminality could be established.
“I did not expect we would see an effect, much less a substantive effect and even less likely a highly resilient effect,” says Wright. “The fact that we are able to detect the effects from childhood exposures now into adulthood stands as a testament of lead’s power to influence behavior over a long period of time.”
Public release date: 27-May-2008
US reporters often do a poor job of reporting about new medical treatments
Most medical news stories about health interventions fail to adequately address costs, harms, benefits, the quality of evidence, and the existence of other treatment options, finds a new analysis in this week’s PLoS Medicine. The analysis was conducted by Gary Schwitzer from the University of Minnesota School of Journalism and Mass Communication.
Schwitzer publishes an online project called HealthNewsReview.org (www.HealthNewsReview.org) that evaluates and grades media stories about new health interventions, notifying journalists of their grades. The project monitors news coverage by the top 50 most widely circulated newspapers in the US; the most widely used wire service (Associated Press); the three leading newsweekly magazines—TIME, Newsweek, and U.S. News & World Report; and the ABC, CBS and NBC television network morning and evening newscasts. Each news story is given a grade from 1 to 10, according to a set of criteria that include whether a story adequately quantifies the benefits of an intervention, appraises the supporting evidence, and gives information on the sources of a story and the sources’ competing interests.
For his analysis in PLoS Medicine, Schwitzer reviewed the ratings for 500 US health news stories that were published or aired over a period of almost two years, and found that 62%–77% of stories had major failings in the quality of reporting. Schwitzer gives examples of particularly poor reporting. ABC World News, for example, was graded only 2 out of 10 for a TV report about a new test for prostate cancer, a test that the show claimed was “more accurate” than existing tests. This poor grade reflected the fact that ABC World News failed to discuss the enormous controversies surrounding the risks and benefits of prostate cancer screening, failed to discuss any evidence that the new test was superior, and failed to mention that the principal investigator of the new test receives a share of the royalties received on sales of the test.
The high rate of inadequate reporting found in this study, says Schwitzer, “raises important questions about the quality of the information US consumers receive from the news media on these health news topics.”
In an editorial discussing the analysis, the PLoS Medicine editors explore some of the reasons why the quality of health news reporting is often poor, including reporters’ inadequate training in understanding health research, the tendency of the 24-hour news cycle towards sensationalism, and the “complicit collaboration” between scientists, reporters, and medical journals in hyping a new study.
“Schwitzer’s alarming report card of the trouble with medical news stories is a wake-up call,” say the editors “for all of us involved in disseminating health research—researchers, academic institutions, journal editors, reporters, and media organizations—to work collaboratively to improve the standards of health reporting.”
CITATION: Schwitzer G (2008) How do US journalists cover treatments, tests, products, and procedures” An evaluation of 500 stories. PLoS Med 5(5): e95.
Public release date: 27-May-2008
People with ADHD do 1 month’s less work per year
Workers with attention deficit hyperactivity disorder (ADHD) do 22 days less work per year than people who do not have the disorder, finds research published online ahead of print in Occupational and Environmental Medicine.
So much work is being lost that the researchers recommend employers consider screening staff for ADHD and providing treatment for those affected, because it would be more cost-effective for their businesses.
People who have ADHD find it difficult to concentrate because they may be hyperactive, easily distracted, forgetful or impulsive. Children with the disorder are being increasingly diagnosed because they are likely to be tested for ADHD if they have problems with their schoolwork. However, many adults with ADHD do not know they have the condition.
More than 7,000 employed and self-employed workers aged 18-44 years were screened for ADHD as part of the World Health Organisation World Mental Health Survey Initiative. They were also asked about their performance at work in the last month.
On average 3.5 per cent of workers had ADHD. It was more prevalent in men and workers in developed rather than developing countries.
People with ADHD were found to spend 22.1 more days not doing work than other workers per year. This was made up of 8.4 days when they were unable to work or carry out their normal activities, plus 21.7 days of reduced work quantity and 13.6 days of reduced work quality.
The researchers, who are part of a WHO research consortium at Harvard Medical School, suggest adult ADHD might be a candidate for targeted workplace screening and treatment programmes because cost-effective therapies exist which could improve some aspects of affected workers’ performance. “It might be cost-effective from the employer perspective to implement workplace screening programmes and provide treatment for workers with ADHD,” they say.
Ralphs Note – What a wonderful world it will be, when we all think and act alike. Thank You Harvard, and the WHO, for introducing me to the world of Biological Fascism.
Public release date: 27-May-2008
Combining exercise with hormone could prevent weight gain
GAINESVILLE, Fla. — Once heralded as a promising obesity treatment, the hormone leptin lost its fat-fighting luster when scientists discovered overweight patients were resistant to its effects. But pairing leptin with just a minor amount of exercise seems to revive the hormone’s ability to fight fat again, University of Florida researchers recently discovered.
The combination of leptin and a modest dose of wheel running prevented obese rats on a belt-busting, high-fat diet from gaining weight, even though neither tactic worked alone, say UF researchers, writing in the journal Diabetes.
“They don’t run enough to use sufficient energy to prevent weight gain,” said Philip Scarpace, Ph.D., a professor of pharmacology and therapeutics in the UF College of Medicine and the senior author of the study. “What the act of running appears to do is allow the leptin to work again. It’s a demonstration that this simple act can reverse leptin resistance.”
More than 34 percent of American adults — about 72 million people — are obese or overweight, according to the Centers for Disease Control and Prevention. Scientists had hoped to wield leptin, a hormone that sends the body chemical signals to stop eating and use stored energy, as a weight-loss weapon. Studies in lean animals were promising, but overweight animals and people don’t respond the same way, likely because their bodies already overproduce leptin, causing them to develop resistance to the hormone, Scarpace said.
“Obese animals and humans don’t respond to leptin at all,” he said. “Our lab is interested in elucidating why this is the case. We know that often single-entity treatments are not successful. The concept was maybe a dual-entity treatment would work.”
To test this, the researchers decided to pair leptin with exercise, comparing the effects on both normal-weight and obese rats kept on high-fat diets, which simulate the type of fast-food-filled fare many Americans eat.
The rats were further separated into three groups to test three approaches. One group received leptin, another group got an exercise wheel and the third group got both leptin and a wheel. In the normal-weight rats, leptin and exercise both worked to prevent weight gain. The normal-weight rats ran significantly more than their bulkier peers, logging in about two and a half miles a day on their wheels, and kept off weight proportionally to how much they ran. The rats were allowed to run as much as they chose.
In the obese rats, which ran six to eight times less, neither running nor leptin alone kept the weight from accruing. Giving the rats leptin actually caused them to gain more weight than eating a high-fat diet alone, the study shows.
“This is a startling finding. Leptin is expected to reduce body weight, not promote weight and fat gain,” Scarpace said.
But the obese rats that ran and took leptin kept the extra weight off, Scarpace said. More research is needed to understand exactly why this combination works, but the scientists speculate that the low level of running triggered a metabolic change in the rats that cleared the way for the leptin signal to get through.
“They should have been gaining weight,” Scarpace said. “They don’t run enough to make any difference.”
Christopher Morrison, Ph.D., an assistant professor at the Pennington Biomedical Research Center at Louisiana State University who wrote a commentary about the UF study in Diabetes, said he thinks the discovery has potential to help combat obesity in humans.
“That’s the hope and the reason for doing this type of work,” he said. “The study raises many questions. If we can improve leptin sensitivity and enhance the ability of the signal to get through, maybe it will lead to weight loss.”
UF researchers are now aiming to team with doctors and test the leptin and exercise combination in humans. They also are working on additional studies to better understand leptin’s effects and its signaling pathway. Scientists still can’t pinpoint exactly why overweight people develop resistance to leptin and what role the hormone really plays in obesity.
“Leptin may be the cause of obesity rather than a cure,” Scarpace said. “Unless you run.”
Ralph’s Note – Keep this is mind, if you use colostrum
Public Release: 27-May-2008
Estrogen Helps Drive Distinct, Aggressive Form of Prostate Cancer
NEW YORK (May 27, 2008) — Using a breakthrough technology, researchers led by a Weill Cornell Medical College scientist have pinpointed the hormone estrogen as a key player in about half of all prostate cancers.
Estrogen-linked signaling helps drive a discrete and aggressive form of the disease caused by a chromosomal translocation, which in turn results in the fusion of two genes.
“Fifty percent of prostate cancers harbor a common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumors,” explains study senior author Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College. Dr. Rubin is also attending pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
“Interfering with this gene fusion — or its downstream molecular pathways — will be crucial in the search for drugs that fight the disease. Based on our new data, we now believe that inhibiting estrogen may be one way of doing so,” he says.
The findings are published in the May 27 online edition of the Journal of the National Cancer Institute. Dr. Rubin conducted the study while at the Brigham and Women’s Hospital and in collaboration with Dr. Todd Golub and other members of the Broad Institute of MIT and Harvard, in Cambridge, Mass. His team is now continuing this line of research at Weill Cornell.
Dr. Rubin, along with researchers at the University of Michigan, first discovered and described the common fusions between the TMPRSS2 and ETS family member genes subset of prostate cancer in the journal Science in 2005. “The discovery showed that these malignancies occur after an androgen (male hormone)-dependent gene fuses with an oncogene — a type of gene that causes cancer,” he explains.
Experts have long understood that male hormones help spur prostate cancer — in fact, androgen-deprivation therapy is a first-line treatment against the disease. And yet the disease can progress despite androgen reduction, suggesting that other pathways might be at work.
“So, we wanted to learn more — what is the genetic and molecular ‘fingerprint’ of this aggressive subset of prostate tumor?” Dr. Rubin says.
Answering that question required the analysis of 455 prostate cancer samples from trials in Sweden and the United States that were conducted as far back as the mid-1970s.
“These samples were placed in fixative and not frozen, so we needed new methods of retrieving the genetic information,” Dr. Rubin says. To do so, his team led by co-lead authors Dr. Sunita Setlur and Dr. Kirsten Mertz developed an innovative technology for effectively “reading” the gene transcription profiles hidden in the samples.
“That led us to perform the largest gene-expression microarray analysis yet conducted in prostate cancer research, amassing information on more than 6,000 genes,” Dr. Rubin says. “This allowed us to obtain a robust, 87-gene expression ‘signature’ that distinguishes fusion-positive TMPRSS2-ERG cancers from other prostate malignancies.”
A close analysis of the signature yielded a surprise: that estrogen-dependent molecular pathways appear to play a crucial role in regulating (and encouraging) this aggressive subset of prostate cancer.
While estrogen is typically thought of as a “female” hormone, men produce it as well.
“Now, we show for the first time that this natural estrogen can stimulate the production of the cancer-linked TMPRSS2-ERG transcript, via the estrogen receptor (ER)-alpha and ER-beta. These receptors are found on the surface of some prostate cancer cells,” Dr. Rubin explains.
The finding could have implications for prostate cancer research, including drug development. According to Dr. Rubin, “We now believe that agents that dampen estrogen activity (ER-alpha antagonists) could inhibit fusion-positive prostate cancers. Alternatively, any intervention that boosts estrogen activity (ER-alpha) might also give a boost to these aggressive malignancies.”
Research into just why fusion-positive prostate cancers are so aggressive — and potential molecular drug targets to help curb that aggression — will continue under Dr. Rubin’s direction at Weill Cornell, in collaboration with members of his group and with computational biologist Dr. Francesca Demichelis.
“The technological achievement of using fixed samples that were up to 30 years old is significant,” Dr. Rubin says. “In the future, we hope to explore banked tissues from clinical trials to help understand why they failed. This should lead to insight for designing the next trial.”
This work was funded by the U.S. National Institutes of Health, a Prostate SPORE grant at the Dana-Farber/Harvard Cancer Center, Swiss Foundation for Medical-Biological Grants SSMBS, U.S. Department of Defense and the Prostate Cancer Foundation.
Ralph’s Note – WoW, Estrogen a driving force. Just Discovered it, hmmm. These the same people who said Testosterone causes prostate cancer? Sounds just like someone is trying to grab credit for other scientist work with xenoestrogens. Next week, maybe they will discover penicillin.
Public release date: 27-May-2008
New breathing exercises help manage asthma
A presentation that demonstrates breathing exercises designed to help reduce the use of asthma inhalers is today available to the general public for free from the Cooperative Research Centre (CRC) for Asthma and Airways website.
The 40 minute production is in response to a research paper on the management of asthma through the use of breathing exercises, conducted by researchers and doctors at Sydney’s Woolcock Institute of Medical Research and Melbourne’s Alfred Hospital, which was published in the August 20061 edition of Thorax.
The results of this study showed that asthmatics who undertook regular breathing exercises reduced their preventer medication levels by up to half and reliever use by up to 86%.
The presentation demonstrates the breathing exercise techniques used in the study and features Professor Christine Jenkins, Head of Asthma Research at the Woolcock Institute and Project Leader of the research study.
In the presentation, she outlines our current understanding of asthma, and the potential role of breathing techniques in helping to control asthma symptoms. She puts this into the context of good asthma management and review. Two different groups of breathing techniques are demonstrated. One set is for practicing daily and one set is for relief of asthma symptoms.
Professor Christine Jenkins, Head of Asthma Research at the Woolcock Institute said, “The research study was designed to measure the effect of two very different exercise regimes on a person’s asthma symptoms, lung function, use of medication and quality of life”.
“However it found no evidence to favour one breathing technique over the other. Instead, both groups of exercises were associated with a dramatic reduction in reliever use. Using either type of exercise was effective in markedly reducing the use of reliever medication. A reduction in inhaled corticosteroid (ICS) dose was also achieved, probably resulting from trial participation and clinical care in the study.”
According to Professor Jenkins the results of regularly undertaking the exercises could be particularly beneficial to the management of patients with mild asthma symptoms, who use a reliever frequently,
“Our study suggests that breathing exercises as a first-line symptom treatment can help to reinforce the message of relaxation and self-efficacy and provide a deferral strategy for beta-agonist use.
“The presentation advises a person to do the exercises twice a day and also whenever they experience asthma symptoms,” she said.
“We hope that people with asthma will avail themselves of the information, presented in this easily understood format, and see it as a complementary approach to their asthma management.”
Public release date: 28-May-2008
Intestinal bacteria promote — and prevent — inflammatory bowel disease
BOSTON, Mass. (May 28, 2008)—Scientists search for drug candidates in some very unlikely places. Not only do they churn out synthetic compounds in industrial-scale laboratories, but they also scour coral reefs and scrape tree bark in the hope of stumbling upon an unsuspecting molecule that just might turn into next year’s big block buster. But one region that scientists have not been searching is their guts. Literally.
Now, a team of researchers at Harvard Medical School, Brigham and Women’s Hospital, and the California Institute of Technology have demonstrated that a molecule produced by bacteria in the gut’s intestinal microflora can eliminate symptoms of inflammatory bowel disease (IBD), a condition that includes Crohn’s disease and ulcerative colitis, in animal models.
“Given the sheer number of bacteria in the gut, the potential for discovering new molecules that can treat a whole range of these diseases is promising,” says Dennis Kasper, co-lead author on the study, professor of medicine and microbiology and molecular genetics at Harvard Medical School, and director of the Channing Laboratory at Brigham and Women’s Hospital.
The study will appear as the cover story in the May 29 issue of Nature.
Scientists have known for many decades that the mammalian gut is an ecosystem teeming with approximately 1,000 different species of bacteria, species as distinct from the host as a single-cell amoeba in pond scum. Rather than causing disease, these bacteria are responsible for protecting against infection and aiding digestion. An increasing number of scientists also suspect that recent increases in asthma and even certain food allergies are caused by disruptions in the delicate balance of this intestinal ecosystem.
In 2005, Kasper and Sarkis Mazmanian, then a postdoc in Kasper’s lab and now an assistant professor of biology at the California Institute of Technology, discovered that a species of intestinal bacteria called Bacteroides fragilis could restore immune system balance in mice that were bred to lack intestinal bacteria. A particular product of B. fragilis, a sugar molecule called polysaccharide A (PSA), recovered the equilibrium of a certain subclass of immune system cells (called Th1 and Th2) whose levels became skewed when bacteria in the gut were absent. The researchers referred to PSA as a “symbiosis factor,” one that established a beneficial link between bacteria and mammals. This was the first study in which such a link was demonstrated.
Interestingly, when the study was completed, Kasper and Mazmanian found in these mice an abundance of immune system cells that were known to protect against colitis and Crohn’s disease. In the current report, the groups decided to expand these findings and explore potential links between PSA and inflammatory bowel disease.
When immunocompromised mice with a specific pathogen-free microbiota were given an intestinal bacterium called Helicobacter hepaticus, they soon developed “rip roaring” IBD, according to Kasper. However, when Helicobacter was combined with B. fragilis, the mice were fine. Further experiments revealed that PSA—the special sugar molecule—was the key factor in preventing IBD. In fact, when mice were given Helicobacter combined with PSA purified from B. fragilis bacteria, they showed no symptoms of IBD.
“But then the key question was, if PSA was essential for preventing these animals from coming down with either colitis or Crohn’s, how did it do it”” says Kasper. “What was the mechanism””
The answer came by studying a subset of interleukins, that is, molecules secreted by immune cells.
Previous studies had shown that two particular interleukins, called IL-17 and IL-23, promote intestinal inflammation and are present at high levels in IBD patients. Here, while the researchers found IL-17 and IL-23 in the guts of animals who had received Heliobacter alone, these interleukins were absent from animals who had also received both PSA-producing B. fragilis and purified PSA.
“We realized that something in PSA must be preventing the inflammation that causes colitis and Crohn’s, which would explain the reduction in IL-17 and IL-23,” says Kasper.
This hunch brought the researchers to consider a third interleukin, IL-10. The opposite of IL-17 and IL-23, IL-10 is anti-inflammatory and had previously been shown to protect against experimental colitis.
The researchers once again administered Helicobacter and PSA-active B. fragilis (the combination that had previously led to healthy mice), only this time they included an antibody that blocked IL-10. As a result, the mice all came down with IBD.
“This demonstrated for us the mechanism by which PSA protects against IBD,” says Kasper.
Indeed, the researchers deduced that PSA prompts immune system cells to secrete IL-10, which in turn suppresses the inflammation caused by IBD. In other words, PSA is an anti-inflammatory.
This research should encourage people (including many scientists) to consider the vast potential for beneficial contributions to human health by “good” bacteria. And what’s more, “This is the first time that a beneficial molecule produced by intestinal bacteria has been shown to work therapeutically in an animal model,” says Mazmanian.
The researchers caution that these findings do not promise any near-term treatments for IBD. “PSA might do the same thing in humans, and it might not,” says Kasper.
However, the mechanism that they’ve discovered should persuade scientists and drug manufacturers to consider new sources for expanding the drug pipeline.
“There is currently no effort to develop molecules that are naturally made by bacteria to use therapeutically,” continues Mazmanian. “This study opens up that possibility.”
Public release date: 28-May-2008
New vegetarian food with several benefits
A new vegetarian food that boosts the uptake of iron and offers a good set of proteins. This could be the result of a doctoral dissertation by Charlotte Eklund-Jonsson at the Department of Food Science.
The food, called tempe, is moreover a whole-grain product with high folate content. It is generally accepted in medicine that whole-grains reduce the risk of cardiovascular diseases, and it is also believed that it protects against age-related diabetes and certain forms of cancer. The B vitamin folate is the natural form of folic acid and, among other things, is necessary for normal fetal development.
“Tempe is designed for vegetarians, but also for people who want to eat less meat for environmental reasons, for example,” says Charlotte Eklund-Jonsson.
“We also had the environment in mind when we chose to base it on barley and oats, which are suitable to cultivate in Sweden and therefore do not require long transports.”
Tempe is produced through fermentation with the aid of the micro fungus Rhizopus oligosporus. Tempe fermentation originates from Indonesia, but soybeans are used as the raw material there.
In her work, Charlotte Eklund-Jonsson developed methods to preserve the high fiber content of the cereal grains and at the same time to enhance their content of easily accessible iron. Normally these two considerations work against each other.
The findings show that the uptake of iron doubled after a meal of barley tempe compared with unfermented barley. In other studies both oat and barley tempe moreover produced low blood sugar responses and insulin responses, which is typical of whole-grain products.
The dissertation is titled “Nutritional properties of tempe fermented whole-grain barley and oats - Influence of processing conditions on the retention and availability of iron, starch and folates” will be publicly defended on June 5 at 10:00 a.m. in Hall KB, kemigården 4, Chalmers University of Technology, Göteborg, Sweden.
Public release date: 28-May-2008
Pycnogenol improved diabetes control and reduced antihypertensive medications
A new study published in the May 2008 (volume 8, issue 25) edition of the journal of Nutrition Research shows Pycnogenol (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, reduces blood sugar in type II diabetes patients, allows people to lower their antihypertensive medication and improves cardiovascular disease (CVD) risk factors. The study, conducted at the University of Arizona, Tucson, indicates Pycnogenol may serve as a potent adjunct to prescription medications for the 20 million people in the Unites States living with diabetes.
“Most people with type II diabetes have cholesterol problems and half of those people experience hypertension. It has been documented that Pycnogenol mediates a number of beneficial effects on the cardiovascular system for diabetics and healthy individuals,” said Dr. Ronald Watson, a lead researcher of the study. “Previous studies have shown Pycnogenol supplementation to be associated with reducing platelet aggregation, lowering LDL and increasing HDL cholesterol and modifying hypertension, among others. But what really makes the study results compelling is Pycnogenol simultaneously lowered blood glucose, LDL cholesterol and blood pressure in patients. Furthermore, this is the first study suggesting that Pycnogenol might also be beneficial in protecting kidney function in diabetics.”
The 12-week, randomized, double-blind, placebo-controlled trial consisted of 48 men and women, 40 to 75 years of age, with noninsulin-dependent type II diabetes, taking anti-diabetic medication with metformin, sulfonylurea and glitazones. Furthermore, they took antihypertensive medications with ACE inhibitors such as Lisinopril. Despite their medication their fasting blood sugar was above healthy values (142 mg/dL) and their average systolic blood pressure was 139 mmHg subjects were randomly assigned to receive either Pycnogenol (25 mg, 5 times daily) or matched placebo. Participants were instructed to continue taking their prescription medications.
Blood pressure and heart rate were recorded at baseline and at biweekly follow-up visits physicians tried to lower the patient’s individual anti-hypertensive medication with aim to keep it below 130 mmHg. At monthly follow-up visits, all unused prescription medications were collected and counted. Change from baseline at weeks four, eight and 12 were calculated after eight hours of fasting for assessing plasma glucose, LDL cholesterol and endothelin-1. Urinary protein concentration was measured from spot urine samples on a monthly basis.
In the Pycnogenol treated groups, results revealed Pycnogenol achieved blood pressure control in 58.3 percent of patients at the end of the 12 weeks with 50 percent reduction in prescription medications. Plasma endothelin-1, a very potent hormone-like arterial constrictor which is typically elevated in diabetes patients, decreased by 17.8 percent. The constriction of arteries is believed to be the cause of hypertension and the decreased endothelin-1 with Pycnogenol is suggested to be the cause for the healthier blood pressure. The mean average blood glucose decreased from high 142.3 mg/dL to a healthy value 118.6, a decrease by 16.7% after 12 weeks. Low-density lipoprotein cholesterol improved significantly, declining by 11.9%.
“It is amazing to see that adding Pycnogenol to the regimen of prescription medication brought blood glucose to healthy levels, allowed half the patients to reach healthy blood pressure and enabled 58% to even lower their anti-hypertensive medication,” said Watson. “An absolutely new finding is that Pycnogenol appears to improve kidney function in diabetic people, this deserves more attention in future investigations. Pycnogenol should be standard adjunct to pharmaceutical treatment of diabetic patients to help control an array of cardiovascular problems.”
In the past four years alone, numerous studies have been published on Pycnogenol’s health benefits for people living with diabetes. In a study published in the March 2004 Diabetes Care, Pycnogenol was shown to lower blood sugar levels and not affect insulin levels. The October 2006 journal of Angiology revealed Pycnogenol reduces diabetic microangiopathy and in 2006, published research in the July journal of Clinical and Applied Thrombosis/Hemostasis revealed Pycnogenol heals leg ulcers in patients who suffer from diabetic leg ulcerations. Additionally, Pycnogenol has been shown to reduce fasting and postprandial serum glucose levels and glycosylated hemoglobin in patients with type II diabetes. And, earlier studies with more than 1,000 diabetes patients, showed that Pycnogenol has the ability to seal leaky capillaries in the eye. This capability stops the progression of vision loss in patients suffering from diabetic retinopathy, a diabetes-induced eye disease that ultimately leads to blindness.
Public release date: 29-May-2008
Dehydrated tomatoes show promise for preventing prostate cancer
PHILADELPHIA – New research suggests that the form of tomato product one eats could be the key to unlocking its prostate cancer-fighting potential, according to a report in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research.
“Processing of many edible plants through heating, grinding, mixing or drying dramatically increases their nutrition value, including their cancer prevention potential. It appears that the greatest protective effect from tomatoes comes by rehydrating tomato powder into tomato paste,” said Valeri V. Mossine, Ph.D., research assistant professor of biochemistry at the University of Missouri.
The protective effect of tomato products against prostate cancer has been suggested in many studies, but researchers remain uncertain about the exact mechanisms. Mossine and colleagues demonstrated that FruHis, an organic carbohydrate present in dehydrated tomato products, exerts a strong protective effect.
Researchers divided rats into groups of 20 and fed them a control diet or a diet that included tomato paste, tomato powder or tomato paste plus additional FruHis. All animals were then injected with prostate cancer-causing chemicals.
Animals fed the tomato paste plus FruHis diet had the longest survival from cancer at 51 weeks compared with 50 weeks in the tomato powder group, 45 weeks in the tomato paste alone group and 40 weeks in the control group.
On post-mortem exam, prostate tumors were found in 10 percent of the rats that had been given a combination of tomato paste and FruHis, compared with 30 percent of animals in the tomato powder group, 25 percent in the tomato paste alone group and 60 percent in the control group.
Mossine said the protective effect of tomato-based products was restricted to prostate tumors, which is consistent with other research on tomatoes and cancer. Incidence of other tumors was too small to examine.
In vitro, Mossine and colleagues evaluated the anti-cancer properties of FruHis and 14 other D-fructose amino acids and found that FruHis in a concentrated form protected against DNA damage known to lead to prostate cancer. When combined with lycopene, FruHis stopped cancerous cell growth more than 98 percent of the time.
“Before this study, researchers attributed the protective effect of tomatoes to ascorbic acid, carotenoids, or phenolic compounds,” Mossine said. “FruHis may represent a novel type of potential dietary antioxidant. Experiments like these suggest that a combination of FruHis and lycopene should be investigated as a potential therapeutic anti-tumor agent, not just a prevention strategy.”
Although Mossine cautioned against drawing broad conclusions from this animal study, he said, “the result may introduce an additional intrigue into an ongoing dispute over the beneficial effects of dietary lycopene and tomato products in lowering the risk of prostate cancer. Human trials are certainly warranted.”
Public release date: 29-May-2008
Exercise cuts cancer death in men
[PRESS RELEASE, 29 May 2008] Men who exercise often are less likely to die from cancer than those who don’t exercise, according to a new study from the Swedish medical university Karolinska Institutet. In the study, the researchers looked at the effect of physical activity and cancer risk in 40,708 men aged between 45 and 79.
Over the seven year period of the study, published in the British Journal of Cancer, 3,714 men developed cancer and 1,153 died from the disease. Men who walked or cycled for at least 30 minutes a day had an increased survival from cancer with 33 per cent, than the men who exercised less or did nothing at all. The researchers also found that a more extensive programme of walking and cycling for between 60 and 90 minutes and a day, led to a l6 per cent lower incidence of cancer. But these activities only led to a five per cent reduction in cancer rates among the men who walked or cycled for 30 minutes day, a finding which could be due to chance.
The researchers surveyed men from two counties in central Sweden about their lifestyle and the amount of physical activity they did. They then scored these responses and compared the results with data officially recorded in a central cancer registry over a seven year period.
“These results show for the first time, the affect that daily exercise has in reducing cancer death risk in men aged between 45 and 79”, says Professor Alicja Wolk, who led the study. “We looked at more moderate exercise such as housework, undertaken over a longer period of time and found that this also reduced men’s chances of dying from the disease.”
Public release date: 30-May-2008
US soldiers in high-tuberculosis areas face new epidemic: false positives
U.S. Army service members are increasingly deployed in regions of the world where tuberculosis (TB) is rampant, such as Iraq and Afghanistan, and the military now faces a growing medical problem. But it is not TB itself that is on the rise—instead, the problem lies with the growing number of “pseudoepidemics,” or clusters of false-positives for TB that are the result of universal testing with a notoriously inaccurate tuberculin skin test (TST) and inconsistent procedures for interpreting those tests in low-risk populations.
These false positives tests have become more than a mere institutional inconvenience or a momentary medical scare for Soldiers being tested. They are a real financial and medical burden because they inappropriately diverting limited funds and resources.
A recent study, published in American Thoracic Society’s first issue for June of the American Journal of Respiratory and Critical Care Medicine, describes eight outbreaks of false-positive TB tests between 1983 and 2005. The study was led by U.S. Army Major James Mancuso, M.D., of the Uniformed Services University of the Health Sciences.
Recent deployments to Iraq and Afghanistan, which are reported to have among the highest rates of active TB in the world, have raised concerns about TB exposure. However, many service members do not have sufficient contact with locals to raise their risk of contracting TB. As a consequence, “testing after recent deployments to the endemic and hyperendemic areas has occasionally resulted in large numbers of U.S. Army service members with [positive tests] and massive efforts aimed at preventing active TB,” wrote Dr. Mancuso.
Because the positive-predictive value of a test—that is, the likelihood of a positive result indicating an actual case—is dependent on the prevalence of disease in a population. The lower the prevalence of a disease, and the higher the variability in the test and testing procedures, the less the positive-predictive value of a test will be. “This may dramatically reduce the positive-predictive value of the test to below 50 percent,” said Dr. Mancuso.
Dr. Mancuso and his colleagues conducted outbreak investigations in deployed locations such as the Balkans and Afghanistan, where they collected and reviewed medical records of reported active and latent TB cases in deployed U.S. Army service members. They then obtained the medical histories of these soldiers, including prior diagnoses and treatments, determined current symptoms and interviewed the subjects to identify other possible risk factors. Finally, they retested all available skin test converters.
“Repeat testing of converters (positives) found that 30 to 100 percent were negative on retesting,” wrote Dr. Mancuso. In one case, 95 percent of positive TB tests (38 of 40 tests) from Army National Guard servicemen in Kosovo were subsequently found to be negative, and the pseudoepidemic was primarily attributed to variability with the test administration and reading, as well as to the specific type of test used.
“The testing of [a] predominantly low-risk population leads to false-positive results in individuals and pseudoepidemics of false-positive TST conversions in U.S. Army populations,” Dr. Mancuso concluded, recommending three actions to reduce the occurrence of false positive skin tests and these apparent outbreaks: test only truly high-risk personnel; standardize testing procedures; and use the more reliable of the TST tests, Tubersol, in lower-risk populations such as the U.S. Army.
“As always, an individualized assessment of each patient’s risk of tuberculosis should be used to target testing and treatment of latent tuberculosis infection. In the absence of other risk factors, clinicians and public health officials should interpret reported skin test conversions after deployment with caution,” he added.
Public release date: 30-May-2008
Whole milk is effective and cost-effective as oral contrast agent
An item commonly found in many homes – whole milk – is just as effective, costs less and is easier on the patient than a diluted (0.1%) barium suspension that is also commonly used as an oral contrast agent in conjunction with CT to examine the gastrointestinal tract, a new study finds.
The study included 215 patients undergoing abdominal and pelvic CT, said Chi Wan Koo, MD, lead author of the study. All patients were given an IV contrast media; 115 were also given whole milk as an oral contrast agent; 100 received a 0.1% barium suspension. Two radiologists reviewed all the images and scored them based on degree of bowel distension and bowel wall visibility. Adequate bowel distension is necessary to optimize resolution of the bowel wall and contents, said Dr. Koo.
The study found that the images taken of patients who were given whole milk were just as useful as the images that were taken of patients given the diluted barium, she said.
In addition, patients were given a questionnaire, asking them how well they tolerated the oral contrast agents, and a cost comparison was done. “We found that milk was less expensive, it had better patient acceptance and fewer adverse symptoms,” Dr. Koo said.
Whole milk and 0.1% barium suspension are valuable in the diagnosis of small bowel disorders, such as ischemia, neoplasm and Crohn’s disease, said Dr. Koo. They are also useful in evaluating pancreatic and biliary abnormalities.
Public release date: 1-Jun-2008
How advanced prostate cancer becomes resistant to androgen-deprivation therapy
SEATTLE – For the past 70 years the treatment of choice for advanced, metastatic prostate cancer has been androgen-deprivation therapy. That is, the suppression of circulating testosterone – the hormone that fuels prostate-cancer growth – via surgical castration (orchiectomy) or medical castration with testosterone-blocking drugs. While such therapy buys time for patients, it is not a cure, as inevitably the cancer becomes resistant to the androgen deprivation and continues to grow.
A team of researchers led by Peter Nelson, M.D., and Elahe (pronounced EL-ah-hay) Mostaghel, M.D., Ph.D., of Fred Hutchinson Cancer Research Center; and R. Bruce Montgomery, M.D., and Paul Lange, M.D., of the University of Washington School of Medicine, in collaboration with other colleagues at UW and Oregon Health Sciences University, has uncovered what may be the key to understanding how prostate tumors eventually become resistant to androgen-deprivation therapy.
“We found that despite the suppression of circulating androgen levels to very low or castrate levels, metastatic prostate tumors are themselves able to maintain significant levels of testosterone, which fuels the growth of the cancer,” said Mostaghel, a clinical-research associate in Nelson’s laboratory, which is based in the Human Biology Division of the Hutchinson Center.
The researchers found that testosterone levels were four times higher in metastatic tumors from castrate men (collected immediately after death via rapid autopsy) than in benign and cancerous prostate tissue in men with normal circulating androgen levels (collected at the time of prostate surgery).
This finding, reported in the June 1 issue of Cancer Research, could lead to the development of better drugs to treat metastatic disease – cancer that has spread beyond the prostate to distant sites throughout the body, such as bone, lymph nodes and internal organs.
“So far we’ve targeted systemic, or circulating, androgens in men with advanced prostate cancer,” Mostaghel said. “What these findings suggest is that we really need to target the metastatic prostate-tumor tissue itself as the source of tumor androgens.”
In addition to measuring androgen levels in distant tumor sites, the researchers analyzed gene-expression patterns in the metastatic tissue to confirm the presence of genetic pathways that control testosterone production. The researchers indeed found within the metastatic tissue the genetic transcripts necessary for making the proteins that produce testosterone and other androgen hormones.
“We not only found that metastatic-tumor tissues have high enough androgen levels within them to support continued growth of the tumor cells, but also a critically important reason behind why those androgens are there – the discovery that the gene pathways for synthesizing androgens from cholesterol appear to be present in the distant tumor sites. This finding will allow us to start honing in on the specific source of those androgens and how we can eliminate them,” Mostaghel said. “As we develop new drug targets, we will need to focus on enzymes that seem to be active in the tumor tissue itself. This offers a new way of looking at hormone suppression. In addition to systemic suppression, it suggests we also need to target hormone suppression much more specifically, inside the tumor itself.” Doing so could improve treatment for patients with all stages of prostate cancer, she said, from men with metastatic disease to men with high-risk, localized tumors in which there is concern that small amounts of cancer may have escaped the prostate.
Mostaghel and colleagues feel the most promising drug targets will be inhibitors of CYP17 enzymes, which disrupt the conversion of progesterone to testosterone precursors, as well as inhibitors of enzymes that perform subsequent steps in testosterone production: AKR1C3 and 17BHSD3.
For the study, the researchers examined soft-tissue prostate-cancer metastases obtained from eight medically or surgically castrated men via the University of Washington rapid-autopsy program, one of a handful of such programs in the nation. For control purposes, the researchers also examined benign and cancerous prostate tissue from eight men who underwent radical prostatectomy for early-stage, localized prostate cancer, and prostate tissue from two men whose prostates were removed for reasons unrelated to prostate cancer.
The researchers also examined metastatic human prostate-cancer cells, obtained from androgen-deprived men, which had been engrafted and allowed to grow in both castrated and non-castrated mice, a process called xenografting.
Androgen levels in the xenograft tumors in the castrated mice, which had no circulating androgen, were actually higher than in the xenograft tumors in the mice that had not been castrated. The researchers found a particularly striking difference in levels of DHT. “We found DHT levels to be twice as high in the castrated mice,” Mostaghel said. “That tells us that the tumor is making testosterone and hanging on to it somehow and is further evidence that metastatic tissue has the capacity to make its own testosterone.”
Each year, approximately 200,000 U.S. men are diagnosed with prostate cancer. While the majority of cases are early-stage, localized disease – due in large part to the widespread use of PSA, or prostate-specific antigen screening – an estimated 50 percent of patients diagnosed and treated for clinically localized prostate cancer will progress to more advanced disease, which kills an estimated 30,000 American men annually.
Public release date: 1-Jun-2008
Bisphenol A: Controversy over widely used plastics chemical spurs product changes, regulatory debate
Chemical & Engineering News
The controversy over bisphenol A (BPA) is spurring manufacturers to offer BPA-free products and fueling debate over how new chemicals enter the market, according to an article scheduled for the June 2 issue of Chemical & Engineering News, ACS’ weekly newsmagazine. Widely used in consumer products, including baby bottles and beverage bottles, BPA has come under increasing scrutiny by Congress, regulators in the U.S. and abroad, the news media, and other groups over its allegedly harmful health effects.
Written by C&EN Associate Editor Britt Erickson, the story points out that retailers and manufacturers alike are not waiting for scientists to settle the unknowns about BPA, which can have estrogen-like biological effects. Instead, they have been pulling BPA products from store shelves or abandoning its use altogether. Consumers also are avoiding products packaged in containers made with BPA.
More than two billion pounds of BPA are used annually in the United States. Although a growing number of studies suggest that low-level exposure to the chemical can cause cancer, obesity, and other health problems, the plastics industry and federal regulatory agencies insist that the chemical is safe, the article states. Erickson described how Congress entered the fray by launching an investigation into the use of BPA in baby bottles.
Public release date: 1-Jun-2008
Vitamins Help Prevent Vision Loss from AMD—If Used Correctly
A study of individuals with age-related macular degeneration (AMD), based at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, found that nearly 40 percent of those likely to benefit from specific vitamin/mineral supplements were either not taking the supplements or not using the recommended dosage. The study also showed that some patients used high-dose supplements even in the absence of evidence that these would be effective for their levels of AMD or other eye conditions. The ophthalmic researchers, led by Susan B. Bressler, M.D., concluded that AMD patients appear to lack a clear understanding of supplement use in AMD treatment, and that “improved patient education may be vital to maximize the potential” of this therapy.
The public health impact could be substantial: in the United States if the appropriate patients used the correct supplements, about 300,000 people could potentially avoid advanced AMD within a five year period. At least eight million Americans are at risk for advanced AMD which can destroy the central vision needed to recognize faces, read, drive and enjoy daily life. In 2001 the Age-Related Eye Disease Study (AREDS) reported findings on its clinical trial that identified a specific formula of antioxidants (vitamin C, vitamin E and beta-carotene) and zinc that reduced the probability of progression to advanced AMD by 25 percent— either the “wet” or central geographic atrophy forms—among individuals at risk. Those who have AMD and smoke may need to use a formula that omits beta-carotene since high doses of this micronutrient have been associated with increased rates of lung cancer and mortality. Though effective treatment for advanced AMD is available, it can be expensive and is limited to the “wet” form. Also, since such treatment may not restore vision already lost to the illness, it remains important to use all effective approaches to preventing AMD progression.
The Wilmer Institute-based study surveyed 332 individuals who identified themselves as having AMD; the median participant age was 79 years. Of these, 228 were considered candidates for benefit from the AREDS formula, but only 140 patients (61 percent) in this group were using the correct formula as recommended. Nearly 50 percent of the candidates-for-benefit did not correctly answer questions on the relevance of vitamin/mineral supplements to their eye condition and how their vision might benefit. But patients who indicated that they partially or fully understood the rationale for supplements were about twice as likely to be using the AREDS formula correctly.
Public release date: 2-Jun-2008
The good news in our DNA: Defects you can fix with vitamins and minerals
Berkeley — As the cost of sequencing a single human genome drops rapidly, with one company predicting a price of $100 per person in five years, soon the only reason not to look at your “personal genome” will be fear of what bad news lies in your genes.
University of California, Berkeley, scientists, however, have found a welcome reason to delve into your genetic heritage: to find the slight genetic flaws that can be fixed with remedies as simple as vitamin or mineral supplements.
“I’m looking for the good news in the human genome,” said Jasper Rine, UC Berkeley professor of molecular and cell biology.
“Headlines for the last 20 years have really been about the triumph of biomedical research in finding disease genes, which is biologically interesting, genetically important and frightening to people who get this information,” Rine said. “I became obsessed with trying to decide if there is some other class of information that will make people want to look at their genome sequence.”
What Rine and colleagues found and report this week in the online early edition of the journal Proceedings of the National Academy of Sciences (PNAS) is that there are many genetic differences that make people’s enzymes less efficient than normal, and that simple supplementation with vitamins can often restore some of these deficient enzymes to full working order.
First author Nicholas Marini, a UC Berkeley research scientist, noted that physicians prescribe vitamins to “cure” many rare and potentially fatal metabolic defects caused by mutations in critical enzymes. But those affected by these metabolic diseases are people with two bad copies, or alleles, of an essential enzyme. Many others may be walking around with only one bad gene, or two copies of slightly defective genes, throwing their enzyme levels off slightly and causing subtle effects that also could be eliminated with vitamin supplements.
“Our studies have convinced us that there is a lot of variation in the population in these enzymes, and a lot of it affects function, and a lot of it is responsive to vitamins,” Marini said. “I wouldn’t be surprised if everybody is going to require a different optimal dose of vitamins based on their genetic makeup, based upon the kind of variance they are harboring in vitamin-dependent enzymes.”
Though this initial study tested the function of human gene variants by transplanting them into yeast cells, where the function of the variants can be accurately assessed, Rine and Marini are confident the results will hold up in humans. Their research, partially supported by the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army, may enable them to employ U.S. soldiers to test the theory that vitamin supplementation can tune up defective enzymes.
“Our soldiers, like top athletes, operate under extreme conditions that may well be limited by their physiology,” Rine said. “We’re now working with the defense department to identify variants of enzymes that are remediable, and ultimately hope to identify troops that have these variants and test whether performance can be enhanced by appropriate supplementation.”
In the PNAS paper, Rine, Marini and their colleagues report on their initial analysis of variants of a human enzyme called methylenetetrahydrofolate reductase, or MTHFR. The enzyme, which requires the B vitamin folate to work properly, plays a key role in synthesizing molecules that go into the nucleotide building blocks of DNA. Some cancer drugs, such as methotrexate, target MTHFR to shut down DNA synthesis and prevent tumor growth.
Using DNA samples from 564 individuals of many races and ethnicities, colleagues at Applied Biosystems of Foster City, Calif., sequenced for each person the two alleles that code for the MTHFR enzyme. Consistent with earlier studies, they found three common variants of the enzyme, but also 11 uncommon variants, each of the latter accounting for less than one percent of the sample.
They then synthesized the gene for each variant of the enzyme, and Marini, Rine and their UC Berkeley colleagues inserted these genes into separate yeast cells in order to judge the activity of each variant. Yeast use many of the same enzymes and cofactor vitamins and minerals as humans and are an excellent model for human metabolism, Rine said.
The researchers found that four different mutations affected the functioning of the human enzyme in yeast. One of these mutations is well known: Nearly 30 percent of the population has one copy, and nine percent has two copies.
The researchers were able to supplement the diet of the cultured yeast with folate, however, and restore full functionality to the most common variant, and to all but one of the less common variants.
Since this experiment, the researchers have found 30 other variants of the MTHFR enzyme and tested about 15 of them, “and more than half interfere with the function of the enzyme, producing a hundred-fold range of enzyme activity. The majority of these can be either partially or completely restored to normal activity by adding more folate. And that is a surprise,” Rine said.
Most scientists think that harmful mutations are disfavored by evolution, but Rine pointed out that this applies only to mutations that affect reproductive fitness. Mutations that affect our health in later years are not efficiently removed by evolution and may remain in our genome forever.
The health effects of tuning up this enzyme in humans are unclear, he said, but folate is already known to protect against birth defects and seems to protect against heart disease and cancer. At least one defect in the MTHFR enzyme produces elevated levels in the blood of the metabolite homocysteine, which is linked to an increased risk of heart disease and stroke, conditions that typically affect people in their post-reproductive years.
“In those people, supplementation of folate in the diet can reduce levels of that metabolite and reduce disease risk,” Marini said.
Marini and Rine estimate that the average person has five rare mutant enzymes, and perhaps other not-so-rare variants, that could be improved with vitamin or mineral supplements.
“There are over 600 human enzymes that use vitamins or minerals as cofactors, and this study reports just what we found by studying one of them,” Rine said. “What this means is that, even if the odds of an individual having a defect in one gene is low, with 600 genes, we are all likely to have some mutations that limit one or more of our enzymes.”
The subtle effects of variation in enzyme activity may well account for conflicting results of some clinical trials, including the confusing data on the effect of vitamin supplements, he noted. In the future, the enzyme profile of research subjects will have to be taken into account in analyzing the outcome of clinical trials.
If one considers not just vitamin-dependent enzymes but all the 30,000 human proteins in the genome, “every individual would harbor approximately 250 deleterious substitutions considering only the low-frequency variants. These numbers suggest that the aggregate incidence of low-frequency variants could have a significant physiological impact,” the researchers wrote in their paper.
All the more reason to poke around in one’s genome, Rine said.
“If you don’t give people a reason to become interested in their genome and to become comfortable with their personal genomic information, then the benefits of much of the biomedical research, which is indexed to particular genetic states, won’t be embraced in a time frame that most people can benefit from,” Rine said. “So, my motivation is partly scientific, partly an education project and, in some ways, a partly political project.”
Marini and Rine credit Bruce Ames, a UC Berkeley professor emeritus of molecular and cell biology now on the research staff at Children’s Hospital Oakland Research Institute, with the research that motivated them to look at enzyme variation. Ames found in the 1970s that many bacteria that could not produce a specific amino acid could do so if given more vitamin B6, and in recent years he has continued exploring the link between micronutrients and health.
“Looked at in one way, Bruce found that you can cure a genetic disease in bacteria by treating it with vitamins,” Rine said. Because the human genome contains about 6 billion DNA base pairs, each one subject to mutation, there could be between 3 and 6 million DNA sequence differences between any two people. Given those numbers, he reasoned that, as in bacteria, “there should be people who are genetically different in terms of the amount of vitamin needed for optimal performance of their enzymes.”
This touches on what Rine considers one of the key biomedical questions today. “Now that we have the complete genome sequences of all the common model organisms, including humans, it’s obvious that the defining challenge of biology in the 21st century is not what the genes are, but what the variation in the genes does,” he said.
Rine, Marini and their colleagues are continuing to study variation in the human MTHFR gene as well as other folate utilizing enzymes, particularly with respect to how defects in these enzymes may lead to birth defects. Rine also is taking advantage of the 1,500 students in his Biology 1A lab course to investigate variants of a second vitamin B6-dependent enzyme, cystathionine beta-synthase.
He also is investigating how enzyme cofactors like vitamins and minerals fix defective enzymes. He suspects that supplements work by acting as chaperones to stabilize the proper folding of the enzyme, which is critical to its catalytic activity. “That is a new principle that may be applicable to drug design,” Rine said.
Public release date: 2-Jun-2008
Is tap water safe for expectant mothers?
Drinking water disinfected by chlorine while pregnant may increase the risk of having children with heart problems, cleft palate or major brain defects, according to a study published today in BioMed Central’s open access journal Environmental Health.
This finding, based on an analysis of nearly 400,000 infants in Taiwan, is the first that links by-products of water chlorination to three specific birth defects.
Water chlorination is a widely used and efficient method to disinfect drinking water and reduce the occurrence of waterborne diseases. However, numerous studies have revealed the presence of many chlorination by-products in the water. Recent research suggests that prenatal exposure to these by-products may increase the risk of birth defects.
A research team led by Jouni Jaakkola from the Institute of Occupational and Environmental Medicine, University of Birmingham, UK, gathered data on almost 400,000 infants born in Taiwan. The researchers used statistical analyses to see if drinking tap water containing high, medium or low levels of chlorination by-products increased the risk of 11 common birth defects.
Although the researchers found no direct link between the prevalence of any birth defect and the level of exposure, their calculations revealed that exposure to high levels of by-products substantially increased the risk of three common defects: ventricular septal defects (holes in the heart), cleft palate, and anencephalus (where neural development fails, resulting in the absence of a major portion of the brain, skull, and scalp).
Exposure to total trihalomethanes above 20 ìg/L was associated with an increased risk of 50 to 100% compared with levels below 5 ìg/L. These results were corroborated by additional analyses, using pooled data from a number of similar studies.
“The biological mechanism for how these disinfection by-products may cause defects are still unknown,” says Jaakkola. “However, our findings don’t just add to the evidence that water chlorination may cause birth defects, but suggest that exposure to chlorination by-products may be responsible some specific and common defects.
Whilst the benefits of water chlorination are quite evident, more research needs to be carried out to determine these side-effects”
Public release date: 3-Jun-2008
Despite vaccine, public should not get complacent about pneumococcal disease
Although the childhood pneumococcal conjugate vaccine has been a boon in reducing the incidence invasive pneumococcal disease (IPD), the public and the medical community must not get complacent, as non-vaccine strains, some resistant to antibiotics, are on the rise, say scientists at a meeting today in Boston.
“We have a vaccine that has dramatically reduced the total burden of pneumococcal disease. It targets 7 strains of the bacteria that were responsible for 90 percent of cases of severe pnuemococcal infection. While that is good news, we still need to be concerned about the replacement strains that are rising to take their place,” says Keith Klugman of Emory University, speaking to the 108th General Meeting of the American Society for Microbiology.
Streptococcus pneumoniae, also called pneumococcus, is one of the most common causes of bacterial pneumonia and deadly bloodstream infections in the United States. It can also cause bacterial meningitis in children and adults. In its less severe forms it commonly causes ear infections. Pneumococcus bacteria can be found colonizing many people’s noses without causing infection. Why it suddenly invades the body and causes disease is unknown.
A vaccine against pneumococcal disease has been available for adults and children over 2 years of age since the 1980s, but in 2000 a new vaccine, known as PCV7, was approved by the FDA for children under 5 years of age.
Since the introduction of PCV7, the Centers for Disease Control and Prevention (CDC) has reported a significant decline in IPD rates among all age levels, but the incidence of IPD caused by strains not included in the vaccine rose by 40%. The most prevalent non-vaccine strain is 19A.
“The PCV7 vaccine contained strain 19F, which is similar to 19A. It was hoped that this would provide some level of protection against 19A. This does not appear to have been the case,” says Klugman.
Of additional concern is the fact that 19A infections are showing up that are resistant to multiple antibiotics. Klugman warns that unncessary antibiotic use driving the development of resistant bacteria and that physicians should prescribe antibiotics only when necessary.
The good news is there is a new vaccine on the horizon, and it contains 13 instead of 7 of the most common pneuococcal strains, including 19A. It is currently in late phase III clinical trials and is most likely to replace PCV7 once it is approved, which could be in the next year or two.
“If we didn’t have PCV13 around the corner, I think our sense of unease would be much greater,” says Klugman.
Ralph’s Note – Did I miss something here? Are we protecting individuals from less dangerous strains. In the end though leaving room for more deadly strains to take its place. This logic would be kind of similar to protecting us from shoplifters. Not realizing the shoplifters were protecting us from the homicidal maniacs..
Public release date: 3-Jun-2008
Agent in red wine found to keep hearts young
MADISON – How, scientists wonder, do the French get away with a clean bill of heart health despite a diet loaded with saturated fats?
The answer to the so-called “French paradox” may be found in red wine. More specifically, it may reside in small doses of resveratrol, a natural constituent of grapes, pomegranates, red wine and other foods, according to a new study by an international team of researchers.
Writing this week (June 3) in the online, open-access journal Public Library of Science One, the researchers report that low doses of resveratrol in the diet of middle-aged mice has a widespread influence on the genetic levers of aging and may confer special protection on the heart.
Specifically, the researchers found that low doses of resveratrol mimic the effects of what is known as caloric restriction – diets with 20-30 percent fewer calories than a typical diet – that in numerous studies has been shown to extend lifespan and blunt the effects of aging.
“This brings down the dose of resveratrol toward the consumption reality mode,” says senior author Richard Weindruch, a University of Wisconsin-Madison professor of medicine and a researcher at the William S. Middleton Memorial Veterans Hospital. “At the same time, it plugs into the biology of caloric restriction.”
Previous research has shown that resveratrol in high doses extends lifespan in invertebrates and prevents early mortality in mice given a high-fat diet. The new study, conducted by researchers from academia and industry, extends those findings, showing that resveratrol in low doses and beginning in middle age can elicit many of the same benefits as a reduced-calorie diet.
“Resveratrol is active in much lower doses than previously thought and mimics a significant fraction of the profile of caloric restriction at the gene expression level,” says Tomas Prolla, a UW-Madison professor of genetics and a senior author of the new report.
The group explored the influence of the agent on heart, muscle and brain by looking for changes in gene expression in those tissues. As animals age, gene expression in the different tissues of the body changes as genes are switched on and off.
In the new study – which compared the genetic crosstalk of animals on a restricted diet with those fed small doses of resveratrol – the similarities were remarkable, explains lead author Jamie Barger of Madison-based LifeGen Technologies. In the heart, for example, there are at least 1,029 genes whose functions change with age, and the organ’s function is known to diminish with age. In animals on a restricted diet, 90 percent of those heart genes experienced altered gene expression profiles, while low doses of resveratrol thwarted age-related change in 92 percent. The new findings, say the study’s authors, were associated with prevention of the decline in heart function associated with aging.
In short, a glass of wine or food or supplements that contain even small doses of resveratrol are likely to represent “a robust intervention in the retardation of cardiac aging,” the authors note.
That finding may also explain the remarkable heart health of people who live in some regions of France where diets are soaked in saturated fats but the incidence of heart disease, a major cause of mortality in the United States, is low. In France, meals are traditionally complemented with a glass of red wine.
The new resveratrol study is also important because it suggests that caloric restriction, which has been widely studied in animals from spiders to humans, and resveratrol may govern the same master genetic pathways related to aging.
“There must be a few master biochemical pathways activated in response to caloric restriction, which in turn activate many other pathways,” explains Prolla. “And resveratrol seems to activate some of these master pathways as well.”
The new findings, according to Weindruch and Prolla, provide strong evidence that resveratrol can improve quality of life through its influence on the different parameters of aging such as cardiac function. However, whether the agent can extend lifespan in ways similar to caloric restriction will require further study, according to the new report’s authors.
Public release date: 3-Jun-2008
Increased Incidence of Melanoma Found in Rheumatoid Arthritis Patients Treated with Methotrexate
A chronic, inflammatory disease of unknown origin, rheumatoid arthritis (RA) affects about 1 percent of adults worldwide. Marked by joint destruction, RA often leads to disability and diminished quality of life. It can also lead to an early death from cancer. Various studies have linked RA to an increased risk of Hodgkin’s and non-Hodgkin’s lymphoma, leukemia, myeloma, and lung cancer. A link between methotrexate (MTX), a disease-modifying antirheumatic drug (DMARD) commonly prescribed to RA patients, and cancer has also been suggested. Numerous case reports of RA patients treated with MTX developing lymphoma and, even more strikingly, tumors disappearing when the drug was discontinued, have prompted concern that MTX itself may be carcinogenic. So far, however, studies addressing this concern have been inconclusive.
To shed further light on the cancer risk for RA patients treated with MTX, researchers in Australia, where RA affects over 2 percent of adults, studied the cancer incidence in RA patients treated with MTX by local doctors. Their findings, featured in the June 2008 issue of Arthritis Care & Research (www.interscience.wiley.com/journal/arthritis), suggest an increased risk of melanoma, as well as other malignancies, for RA patients receiving MTX.
The study focused on 459 RA patients, 309 women and 150 men, regularly seen by 1 of 6 rheumatologists based in Melbourne. All had started treatment with MTX prior to June 1986. The majority had no previous history of immunosuppressant therapy. 61 percent were rheumatoid factor positive. Researchers set out to determine the cancer incidence in these patients compared with the general population and compared with the results of published studies on the incidence of malignancy in MTX-treated RA populations in other countries. For all patients, followup started on the date they first started MTX therapy and ended on the date of their last confirmed doctor visit or death. Over the total of 4,273 person-years of followup, an average of 9.3 years per patient, 87 malignancies were identified.
Researchers then compared the cancer incidence observed among these RA patients with that of their healthy peers in Victoria, Australia. Standard incidence ratios (SRIs) for all malignancies and for selected cancers were calculated using state population cancer rates, stratified by sex, age (in 5 age groups: under 40, 40-49, 50-59, 60-69, and 70 and over), and calendars years, from 1983-1999. Cox regression analysis was also performed, including positive rheumatoid factor and ever use of two immunosuppressive agents, azathioprine and cyclophosphamide.
RA patients exposed to MTX were found to have an estimated 50 percent excess risk of developing cancer in any form. The risk of non-Hodgkin’s lymphoma was more than 5 times higher in RA patients than in the general population. RA patients also had a 3-fold increased risk of melanoma and almost a 3-fold increased risk of lung cancer.
While the increased risk levels for non-Hodgkin’s lymphoma and lung cancer were in line with the findings of related studies in Europe and the United States, the high risk for melanoma stood out as novel. “This study is, to our knowledge, the first to report an increased risk of melanoma in patients with RA treated with MTX compared with the general population,” notes its lead author, Dr. Rachelle Buchbinder.
Interestingly, the researchers observed a 2.5-fold increased cancer risk for MTX-treated RA patients exposed to cyclophosphamide, but contrary to expectation, no increased risk with exposure to azathioprine.
Despite its limitations—lack of a RA control group who was not exposed to MTX, for one—this study has important implications, particularly in regard to the risk of melanoma for RA patients. “Further investigation is needed to determine whether this risk is unique to Australia and what role MTX, immunosuppression per se, and/or environmental factors such as exposure to UV radiation play in its development,” Dr. Buchbinder stresses. “Our findings, taken together with other studies investigating the risk of skin cancer in patients with RA, may support a role for regular skin cancer screening for all patients with RA, particularly those receiving immunosuppressive therapy.”
Article: “Incidence of Melanoma and Other Malignancies Among Rheumatoid Arthritis Patients Treated With Methotrexate,” Rachelle Buchbinder, Melissa Barber, Louise Heuzenroeder, Anita E. Wluka, Graham Giles, Stephen Hall, Andrew Harkness, Daniel Lewis, Geoff Littlejohn, Marian H. Miller, Peter F.J. Ryan, and Damien Jolley, Arthritis & Rheumatism (Arthritis Care & Research), June 15, 2008; 59:6, pp. 794-799.
Public release date: 4-Jun-2008
Long-term pesticide exposure may increase risk of diabetes
Licensed pesticide applicators who used chlorinated pesticides on more than 100 days in their lifetime were at greater risk of diabetes, according to researchers from the National Institutes of Health (NIH). The associations between specific pesticides and incident diabetes ranged from a 20 percent to a 200 percent increase in risk, said the scientists with the NIH’s National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI).
“The results suggest that pesticides may be a contributing factor for diabetes along with known risk factors such as obesity, lack of exercise and having a family history of diabetes,” said Dale Sandler, Ph.D., chief of the Epidemiology Branch at the NIEHS and co-author on the paper. “Although the amount of diabetes explained by pesticides is small, these new findings may extend beyond the pesticide applicators in the study,” Sandler said. Some of the pesticides used by these workers are used by the general population, though the strength and formulation may vary. Other insecticides in this study are no longer available on the market, however, these chemicals persist in the environment and measurable levels may still be detectable in the general population and in food products. For example, chlordane, which was used to treat homes for termites, has not been used since 1988, but can remain in treated homes for many decades. More than half of those studied in the National Health and Nutrition Examination Survey in 1999-2002 had measurable evidence of chlordane exposure. “This is not cause for alarm,” added Sandler “since there is no evidence of health effects at such very low levels of exposure.”
Overall, pesticide applicators in the highest category of lifetime days of use of any pesticide had a small increase in risk for diabetes (17 percent) compared with those in the lowest pesticide use category (0-64 lifetime days). New cases of diabetes were reported by 3.4 percent of those in the lowest pesticide use category compared with 4.6 percent of those in the highest category. Risks were greater when users of specific pesticides were compared with applicators who never applied that chemical. For example, the strongest relationship was found for a chemical called trichlorfon, with an 85 percent increase in risk for frequent and infrequent users and nearly a 250 percent increase for those who used it more than 10 times. In this group, 8.5 percent reported a new diagnosis of diabetes compared with 3.4 percent of those who never used this chemical. Trichlorfon is an organophosphate insecticide classified as a general-use pesticide that is moderately toxic. Previously used to control cockroaches, crickets, bedbugs, fleas, flies and ticks, it is currently used mostly in turf applications, such as maintaining golf courses.
“This is one of the largest studies looking at the potential effects of pesticides on diabetes incidence in adults,” said Freya Kamel, Ph.D., a researcher in the intramural program at NIEHS and co-author in the paper appearing in the May issue of the American Journal of Epidemiology. “It clearly shows that cumulative lifetime exposure is important and not just recent exposure,” said Kamel. Previous cross-sectional studies have used serum samples to show an association between diabetes and some pesticides.
Diabetes occurs when the body fails to produce enough insulin to regulate blood sugar levels or when tissues stop responding to insulin. Nearly 21 million Americans have diabetes. The cause of diabetes continues to be a mystery, although genetics and environmental factors such as obesity and lack of exercise appear to play roles.
To conduct the study, the researchers analyzed data from more than 30,000 licensed pesticide applicators participating in the Agricultural Health Study, a prospective study following the health history of thousands of pesticide applicators and their spouses in North Carolina and Iowa. The 31,787 applicators in this study included those who completed an enrollment survey about lifetime exposure levels, were free of diabetes at enrollment, and updated their medical records during a five-year follow-up phone interview. Among these, 1,171 reported a diagnosis of diabetes in the follow-up interview. The majority of the study participants were non-Hispanic white men.
Researchers compared the pesticide use and other potential risk factors reported by the 1,171 applicators who developed diabetes since enrolling in the study to those who did not develop diabetes. Among the 50 different pesticides the researchers looked at, they found seven specific pesticides — aldrin, chlordane, heptachlor, dichlorvos, trichlorfon, alachlor and cynazine — that increased the likelihood of diabetes among study participants who had ever been exposed to any of these pesticides, and an even greater risk as cumulative days of lifetime exposure increased.
All seven pesticides are chlorinated compounds, including two herbicides, three organochlorine insecticides and two organophosphate pesticides.
“The fact that all seven of these pesticides are chlorinated provides us with an important clue for further research,” said Kamel. Previous studies found that organochlorine insecticides such as chlordane were associated with diabetes or insulin levels. The new study shows that other types of chlorinated pesticides, including some organophosphate insecticides and herbicides, are also associated with diabetes. The researchers also found that study participants who reported mixing herbicides in the military had increased odds of diabetes compared to non-military participants.
Public release date: 5-Jun-2008
Moores UCSD Cancer Center study links vitamin D, type 1 diabetes
Global view supports concept of using vitamin D in reducing disease risks
Sun exposure and vitamin D levels may play a strong role in risk of type 1 diabetes in children, according to new findings by researchers at the Moores Cancer Center at University of California, San Diego (UCSD) and the Department of Family and Preventive Medicine. This association comes on the heels of similar research findings by this same group regarding vitamin D levels and several major cancers.
In this new study, the researchers found that populations living at or near the equator, where there is abundant sunshine (and ultraviolet B irradiance) have low incidence rates of type 1 diabetes. Conversely, populations at higher latitudes, where available sunlight is scarcer, have higher incidence rates. These findings add new support to the concept of a role of vitamin D in reducing risk of this disease.
Ultraviolet B (UVB) exposure triggers photosynthesis of vitamin D3 in the skin. This form of vitamin D also is available through diet and supplements.
“This is the first study, to our knowledge, to show that higher serum levels of vitamin D are associated with reduced incidence rates of type 1 diabetes worldwide,” said Cedric F. Garland, Dr. P.H., professor of Family and Preventive Medicine in the UCSD School of Medicine, and member of the Moores UCSD Cancer Center.
The study is published June 5 in the online version of the scientific journal Diabetologia.
Type 1 diabetes is the second most common chronic disease in children, second only to asthma. Every day, 1.5 million Americans deal with type 1 diabetes and its complications. About 15,000 new cases are diagnosed in the United States each year, where this disease is the main cause of blindness in young and middle-aged adults and is among the top reasons for kidney failure and transplants in youth and midlife.
“This research suggests that childhood type 1 diabetes may be preventable with a modest intake of vitamin D3 (1000 IU/day) for children, ideally with 5 to 10 minutes of sunlight around noontime, when good weather allows,” said Garland. “Infants less than a year old should not be given more than 400 IU per day without consulting a doctor. Hats and dark glasses are a good idea to wear when in the sun at any age, and can be used if the child will tolerate them.”
The association of UVB irradiance to incidence of type 1 diabetes remained strong even after the researchers accounted for per capita healthcare expenditure. This was an important consideration because regions located near the equator tend to have lower per capita healthcare expenditures, which could result in under-reporting of type 1 diabetes.
The researchers created a graph with a vertical axis for diabetes incidence rates, and a horizontal axis for latitude. The latitudes range from -60 for the southern hemisphere, to zero for the equator, to +70 for the northern hemisphere. They then plotted incidence rates for 51 regions according to latitude. The resulting chart was a parabolic curve that looks like a smile.
In the paper the researchers call for public health action to address widespread vitamin D inadequacy in U.S. children.
“This study presents strong epidemiological evidence to suggest that we may be able to prevent new cases of type 1 diabetes,” said Garland. “By preventing this disease, we would prevent its many devastating consequences.”
Public release date: 5-Jun-2008
Another new wrinkle in treating skin aging
Appearing in the June issue of JLR
Topical applications of a naturally occurring fat molecule have the potential to slow down skin aging, whether through natural causes or damage, researchers report.
Through both the normal aging process and external factors like UV damage, smooth, young skin inevitably becomes coarse and wrinkled. The basis of this wrinkling is that time and damage both lower the production of new collagen while increasing the levels of enzymes called MMPs that chew up existing collagen.
Covering up, slowing down, or even stopping the wrinkling process has become a big business, and as part of this research endeavor, Jin Ho Chung and colleagues tested seven naturally occurring lipids (greasy molecules that play many important biological roles) in their ability to reduce skin aging.
In samples of skin cells, three of the lipids could prevent UV-radiation from both reducing collagen expression and increasing the levels of MMPs; they even increased collagen in undamaged skin cells. Of these three, the molecule phosphatidylserine (PS) seemed the most promising, so the researchers tested it on human skin.
They applied a 2% PS solution to small areas of the buttock in both young and old volunteers; the young skin was subsequently given a dose of UV-radiation to simulate sun damage. In both natural and UV-induced aging, PS treatment prevented collagen reduction and an increase in MMPs when compared to no treatment.
While larger and longer trials are needed to confirm any therapeutic benefits, these initial findings suggest topical PA application might be a simple and natural way to slow down the biological elements underlying wrinkling.
Public release date: 9-Jun-2008
Study finds Chinese food good for your heart
Chinese red yeast rice reduces repeat heart attacks/mortality rates
(PHILADELPHIA) – A clinical study on patients who have suffered a heart attack found that a partially purified extract of Chinese red yeast rice, Xuezhikang (XZK), reduced the risk of repeat heart attacks by 45%, revascularization (bypass surgery/angioplasty), cardiovascular mortality and total mortality by one-third and cancer mortality by two-thirds. The multicenter, randomized, double-blind study, was conducted on almost 5,000 patients, ranging in age from 18-70 over a five-year period at over 60 hospitals in the People’s Republic of China. Corresponding author David M. Capuzzi, M.D., Ph.D, director of the Cardiovascular Disease Prevention Program at Jefferson’s Myrna Brind Center of Integrative Medicine and Zonliang Lu, M.D., Ph.D, from the Fuwai Hospital at the Chinese Academy of Medical Science report their findings in the June 15th edition of the American Journal of Cardiology.
“It’s very exciting because this is a natural product and had very few adverse side effects including no abnormal blood changes,” said Capuzzi. “People in the Far East have been taking Chinese red yeast rice as food for thousands of years, but no one has ever studied it clinically in a double-blind manner with a purified product against a placebo group until now and we are pleased with the results. However, people in the United States should know that the commercially available over-the-counter supplement found in your average health food store is not what was studied here. Those over-the-counter supplements are not regulated, so exact amounts of active ingredient are unknown and their efficacy has not been studied yet.”
The study looked at patients who had suffered a heart attack in the previous year. Study participants were given two-300-milligram XZK capsules or a placebo and tracked over a five-year period. The XZK capsules contained a combination of lovastatin, lovastatin hydroxyl acid, ergosterol and other components.
“I think it is surprising that a natural product like XZK would have this great an effect,” said Capuzzi. “If further testing and study prove true, my hope is that XZK becomes an important therapeutic agent to treat cardiovascular disorders and in the prevention of disease whether someone has had a heart attack or not. But it is important to recognize the fact we do not know exactly how Chinese red yeast rice works. The exact ingredients from the XZK capsules have not been isolated and studied yet. Still the results were so profound, even out performing statins prescribed in numerous western populations, that further study should certainly be investigated.”
Ralph’s note – So they don’t know the active ingredients either, but the standard spice worked well.
Public release date: 9-Jun-2008
Men with vitamin D deficiency may have increased risk of heart attack
Low levels of vitamin D appear to be associated with higher risk of myocardial infarction (heart attack) in men, according to a report in the June 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Studies have shown that the rates of cardiovascular disease-related deaths are increased at higher latitudes and during the winter months and are lower at high altitudes, according to background information in the article. “This pattern is consistent with an adverse effect of hypovitaminosis D [vitamin D deficiency], which is more prevalent at higher latitudes, during the winter and at lower altitudes,” the authors write. While other explanations are possible, vitamin D has been shown to affect the body in ways that may influence the risk of heart attack or heart disease.
Edward Giovannucci, M.D., Sc.D., of Harvard School of Public Health and Brigham and Women’s Hospital, Boston, and colleagues reviewed medical records and blood samples of 454 men (age 40 to 75) who had non-fatal heart attack or fatal heart disease from the date of blood collection (between January 1993 and December 1995) until January 2004. They then compared the data from these men with records and blood samples of 900 living men who did not have a history of cardiovascular disease. The men’s diet and lifestyle factors, recorded by self-administered questionnaires were also noted.
Men with a vitamin D deficiency (having 15 nanograms per milliliter of blood or less) had an increased risk for heart attack compared with those with a sufficient amount (having 30 nanograms per milliliter of blood or more) of vitamin D. “After additional adjustment for family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, marine omega 3 intake, low- and high-density lipoprotein cholesterol levels and triglyceride levels, this relationship remained significant,” the authors write. Men with intermediate levels of vitamin D had a higher risk of heart attack than those with sufficient vitamin D levels.
“Vitamin D deficiency has been related to an increasing number of conditions and to total mortality. These results further support an important role for vitamin D in myocardial infarction risk,” the authors conclude. “Thus, the present findings add further support that the current dietary requirements of vitamin D need to be increased to have an effect on circulating 25(OH)D [vitamin D] levels substantially large enough for potential health benefits.”
Public release date: 9-Jun-2008
Eating fish and foods with omega-3 fatty acids linked to lower risk of age-related eye disease
Eating fish and other foods high in omega-3 fatty acids is associated with reduced risk of the eye disease age-related macular degeneration (AMD), according to a meta-analysis of nine previously published studies in the June issue of Archives of Ophthalmology, one of the JAMA/Archives journals. However, the accumulated evidence includes few clinical trials and is insufficient to support the routine consumption of such foods for AMD prevention, the authors note.
“Age-related macular degeneration (AMD) is the leading cause of severe vision loss among elderly people,” they write as background information in the article. New treatments for AMD are potentially risky and treat only certain forms of the disease. “Thus, primary prevention of AMD by modifying risk factors (e.g., cigarette smoking) remains an important public health strategy.”
Elaine W-T. Chong, M.B.B.S., of the University of Melbourne, Australia, and colleagues conducted a systematic review of studies published before May 2007 evaluating the fish consumption and overall omega-3 fatty acid intake for the prevention of AMD. A total of nine studies were identified with 88,974 participants, including 3,203 individuals with AMD.
When results from all nine studies were combined, a high dietary intake of omega-3 fatty acids was associated with a 38 percent reduction in the risk of late (more advanced) AMD, while eating fish twice a week was associated with a reduced risk of both early and late AMD.
“Long-chain omega-3 fatty acids, docosahexaenoic acid in particular, form an integral part of the neural retina,” the layer of nerve cells in the retina, the authors write. Outer cells of the retina are continually shed and regenerated, and deficiencies of omega-3 fatty acids may therefore initiate AMD. “A diet rich in omega-3 fatty acids and fish, as a proxy for long-chain omega-3 fatty acid intake, has therefore been hypothesized as a means to prevent AMD.”
“Although this meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, there is insufficient evidence from the current literature, with few prospective studies and no randomized clinical trials, to support their routine consumption for AMD prevention,” they conclude.
Public release date: 9-Jun-2008
World’s oldest woman had normal brain
Alzheimer’s disease isn’t inevitable, suggests unique case in Neurobiology of Aging
Amsterdam, 9 June 2008 – A 115-year-old woman who remained mentally alert throughout her life had an essentially normal brain, with little or no evidence of Alzheimer’s disease, according to a study in the August issue of Neurobiology of Aging (http://neurobiologyofaging.org/).
The findings question the assumption that Alzheimer’s disease or other forms of dementia will inevitably develop, if people live long enough. “Our observations suggest that, in contrast to general belief, the limits of human cognitive function may extend far beyond the range that is currently enjoyed by most individuals, and that improvements in preventing brain disorders of aging may yield substantial long-term benefits,” according to a study led by Prof. dr. Gert Holstege of University Medical Centre Groningen, The Netherlands.
Dr. Holstege and colleagues had a unique chance to test the mental functioning of one of the world’s oldest humans, and then to compare their findings with the condition of the subject’s brain after death. The patient was a Dutch woman who, at age 82, made arrangements to donate her body to science after death. At age 111, she contacted the researchers to ask whether her body would still be useful for research or teaching purposes. They assured her that, contrary to what she thought, they were especially interested because of her age: “She was very enthusiastic about her being important for science,” Dr. Gert Holstege and colleagues write.
The researchers found the patient to be “an alert and assertive lady, full of interest in the world around her, including national and international politics and sports.” She had lived independently until moving to a residential care home at age 105, mainly because of poor eyesight. Ironically, she had been very small at birth and was not expected to survive.
A series of neurological and psychological examinations were performed when the patient was 112 and 113 years old. The results were essentially normal, with no signs of dementia or problems with memory or attention. In general, her mental performance was above average for adults aged 60 to 75.
As planned, her body was donated to science when she died at age 115. At the time, she was the world’s oldest woman. Examination after death found almost no evidence of atherosclerosis (narrowing of the arteries) anywhere in her body. The brain also showed very few abnormalities—the number of brain cells was similar to that expected in healthy people between 60 and 80 years old.
A key finding was the absence of brain abnormalities typical of Alzheimer’s disease. There were almost no deposits of a substance called beta-amyloid, which are characteristic of Alzheimer’s patients. The other abnormalities present, including “neurofibrillary tangles,” were very mild—too early to cause significant mental impairment.
The unique case lends new insights into the potential for preserving brain function in very elderly patients. Previous studies have found at least mild abnormalities in the brains of nearly all “cognitively normal” elderly people. As the number of people living to age 100 and beyond continues to increase, the findings suggest that deterioration of the brain is not inevitable.
Public release date: 9-Jun-2008
Solid tumor cells not killed by radiation and chemotherapy become stronger
DURHAM, N.C. – Because of the way solid tumors adapt the body’s machinery to bring themselves more oxygen, chemotherapy and radiation may actually make these tumors stronger.
“In a sense, these therapies can make the tumor healthier,” said Mark W. Dewhirst, D.V.M., Ph.D., professor of radiation oncology at Duke University Medical Center. “Unless the treatment is very effective in killing many if not most tumor cells, you are shooting yourself in the foot.”
Dewhirst and colleagues Yiting Cao, M.D., Ph.D., of Duke Pathology, and Benjamin Moeller, M.D., Ph.D. have introduced this counter-intuitive idea at recent conferences and in a review article featured in the June issue of Nature Reviews Cancer.
Radiation and chemotherapy do kill most solid tumor cells, but in the cells that survive, the therapies drive an increase in a regulatory factor called HIF1 (hypoxia-inducible factor 1), which cells use to get the oxygen they need by increasing blood vessel growth into the tumor. Solid tumors generally have low supplies of oxygen, Dewhirst explained and HIF1 helps them get the oxygen they need.
The review article concludes that blocking HIF1 would provide a clear mechanism for killing solid-tumor cells, particularly cells that are proving resistant to radiation or chemotherapy treatments.
As a part of this work, Dewhirst’s team has been studying the phenomenon of rising and falling oxygen levels in tumors, called cycling hypoxia. Oxygen levels have been found to naturally cycle up and down in individual blood vessels as well as large tumor regions. This instability in the tumor’s oxygen levels can increase HIF-1 production and cause radiation therapy to fail, Dewhirst said.
“It is my opinion that the whole tumor grows more aggressively because of this pulsation of oxygen at low levels,” Dewhirst said. “Most people thought cycling hypoxia was caused by temporary stoppage of blood flow in single blood vessel in tumors. In fact, however, oxygen levels cycle up and down virtually everywhere in the tumor, which is caused by fluctuations in blood flow rate. It has been a challenge to convince people of this.”
Dewhirst and colleagues have made movies of oxygen transport in a tumor of a living animal that show the oxygen levels cycle up and down significantly, pulsing in waves seen as color changes in the movies. (View these movies at the Nature Reviews Cancer site: http://www.nature.com/nrc/journal/v8/n6/suppinfo/nrc2397.html )
The Duke team argues that blocking HIF1 is the consistent answer to tumor growth problems. Blocking HIF1 activity interferes with the tumor’s ability to undergo glycolysis (energy production) in low-oxygen conditions, which blocks tumor growth, the authors wrote. Exactly how to accomplish chemotherapy or radiation treatment in the safest, most effective ways, in combination with HIF1 blockade, is still open for exploration, Dewhirst said.
For example, targeting HIF1 in the early stages of tumor growth, especially in very early cancer spread, may help, Dewhirst said. “For a woman who has had a primary breast tumor removed, and who is at high risk for cancer spread, this might be a situation in which you’d target HIF1,” he explained. “Blocking HIF1 makes sense during the early stages of angiogenesis, which is the accelerated phase of blood vessel formation. In this way, you could keep the early metastasis sites inactive and prevent them from growing.”
The Duke team has completed a phase I trial with a HIF1 inhibitor. “We are actively pursuing this clinically and will be moving this study into Phase 2,” Dewhirst said. “We are interested in other applications of HIF-1 inhibition in combination with radiation and chemotherapy for different diseases.”
Public release date: 10-Jun-2008
Common bowel problem linked to chili pepper pain receptor
People with irritable bowel syndrome have a higher than usual number of chilli pepper pain receptors, according to a new study published tomorrow (Wednesday 11 June).
The research, published in the journal Gut, could lead to new therapies for the estimated one in five UK adults who have irritable bowel syndrome (IBS), a painful condition which is poorly understood. Symptoms of IBS include abdominal pain, bloating, and bowel problems such as constipation or diarrhoea.
The new research shows that people with IBS have higher than usual levels of nerve fibres expressing the pain receptor TRPV1, responsible for causing a burning sensation when people eat chilli peppers. The study’s authors, from Imperial College London, hope that doctors could treat the pain that people with IBS experience by targeting and blocking this receptor.
People with severe pain from IBS are currently treated with opiates, which can have serious side-effects. Painkillers such as paracetamol and ibuprofen tend to offer little relief. New painkillers to target TRPV1 are currently being developed by pharmaceutical companies and the new findings suggest that such drugs could tackle some of the symptoms of IBS.
The researchers believe their findings may explain why some people’s IBS symptoms worsen after eating spicy food. They also suggest that the presence of more nerve fibres expressing the TRPV1 pain receptors might mean that people with IBS are more susceptible to pain.
Professor Subrata Ghosh, one of the authors of the study from the Division of Medicine at Imperial College London, said: “IBS can seriously affect people’s quality of life and our new study could explain some of its symptoms. At the moment patients don’t have a lot of options for managing their condition and the treatments we can offer can give disappointing results. We hope that our findings will lead to better treatments to help people with IBS.”
Professor Praveen Anand, an author of the study from the Division of Neuroscience and Mental Health at Imperial College, added: “Up to 50 pharmaceutical and biotech companies world-wide are developing drugs that block the chilli pepper receptor TRPV1, and our published studies on this receptor in a number of chronic pain and hypersensitivity conditions provide hope for millions of suffering patients.”
The researchers reached their conclusions after comparing biopsies of colon tissue taken from 23 patients with IBS and 22 controls, recruited from the Gastroenterology clinics and the endoscopy department at Imperial College Healthcare NHS Trust. The biopsies were studied in the Division of Neuroscience and Mental Health at Imperial College London.