026 Health Research Report 19 MAR 2008
Health Technology Research Synopsis
Health Research Report
26th Issue Date 19 MAR 2008
Compiled By Ralph Turchiano
Editors Top Five:1. Mayo Clinic proceedings highlights research about cardiovascular benefits of omega-3 fatty acids 2. Weight loss more effective than intensive insulin therapy for type 2 diabetics 3. Extra vitamin D in early childhood cuts adult diabetes risk 4. What effect does melatonin have in colitis? 5. Only two per cent of paediatric drug trials reported using independent safety monitoring
In this Issue:
1. Study finds bacteria may reduce risk for kidney stones 2. Type 2 Diabetes May Be Caused by Intestinal Dysfunction 3. When the chips are down — soak them! 4. High levels of estrogen associated with breast cancer recurrence 5. U of I scientists aim to overcome allergic reactions to soy 6. UCLA study finds that broccoli may help boost the aging immune system 7. One small step for man, one giant leap for advertising 8. Curing addiction with cannabis medicines 9. New bacteria contaminate hairspray 10. Oregon study raises questions on synthetic progestins 11. Magnesium associated with lower risk for some strokes in male smokers 12. HPV vaccine reduces abnormal pap test results 13. Mayo Clinic proceedings highlights research about cardiovascular benefits of omega-3 fatty acids 14. Postoperative chemotherapy does not improve survival in gastric cancer patients 15. Weight loss more effective than intensive insulin therapy for type 2 diabetics 16. Study raises caution on new painkillers 17. Is a cup of tea really the answer to everything — even anthrax? 18. Killer fungus spells disaster for wheat 19. Fertility in developing countries: words into action 20. Extra vitamin D in early childhood cuts adult diabetes risk 21. Rodent study finds artificial butter chemical harmful to lungs 22. Study in Circulation Research details how diabetes drives atherosclerosis 23. Legal exposure to asbestos-like material linked to lung damage 25 years later 24. An anti-inflammatory response to the vegan diet 25. Foodborne outbreaks from leafy greens on rise 26. Solving the drug price crisis 27. New study: Pycnogenol improves memory in elderly 28. Pneumococcal disease rates down significantly post-vaccine 29. What effect does melatonin have in colitis? 30. Do bacterial combinations result in enhanced cytokine production? No! 31. Grape skin compound fights the complications of diabetes 32. Scientists successfully awaken sleeping stem cells 33. Only two per cent of paediatric drug trials reported using independent safety monitoring
Public release date: 5-Mar-2008
Study finds bacteria may reduce risk for kidney stones
Boston, MA—Researchers from Boston University’s Slone Epidemiology Center have found that the bacteria Oxalobacter formigenes (O. formigenes), a naturally occurring bacterium that has no known side effects, is associated with a 70 percent reduction in the risk of recurrent kidney stones. These findings appear online in the March issue Journal of the American Society of Nephrology.
Kidney stones are an important health problem in many countries. In the United States, the lifetime risk for developing a stone is five to 15 percent, and a five-year risk for recurrence is 30 to 50 percent. The economic impact of hospital admissions for this condition is $2 billion per year.
According to the researchers, up to 80 percent of kidney stones are predominately composed on calcium oxalate (CaOx) and urinary oxalate is a major risk factor for CaOx stone formation. O. formigenes metabolizes oxalate in the intestinal tract and is present in a large proportion of the normal adult population.
Data was collected in the Boston, Massachusetts and Durham, North Carolina areas from 247 adult patients with recurrent CaOx stones and compared with 259 age, sex, and region-matched controls. O. formigenes colonization was determined by culture of stool samples. Information was obtained by interview and self-administered dietary questionnaire. 24-hour oxalate excretion and other urinary risk factors were measured in a subset of 139 cases and 138 controls. The prevalence of O. formigenes was 17 percent among cases and 38 percent among controls, giving an odds ration of 0.3. The finding was consistent in subgroups defined according to age, sex, race, region and antibiotic use.
“We observed a strong inverse association between colonization with O. formigenes and recurrent CaOx kidney stones, with a 70 percent reduction in overall risk,” said lead researcher David Kaufman, ScD, a professor of epidemiology at Boston University School of Public Health. “Our findings are of potential clinical importance. The possibility of using the bacterium as a probiotic is currently in the early stages of investigation,” added Kaufman
Public release date: 5-Mar-2008
Type 2 Diabetes May Be Caused by Intestinal Dysfunction
NEW YORK (March 5, 2008) — Growing evidence shows that surgery may effectively cure Type 2 diabetes — an approach that not only may change the way the disease is treated, but that introduces a new way of thinking about diabetes. A new article — published in a special supplement to the February issue of Diabetes Care by a leading expert in the emerging field of diabetes surgery — points to the small bowel as the possible site of critical mechanisms for the development of diabetes. The study’s author, Dr. Francesco Rubino of NewYork-Presbyterian Hospital/Weill Cornell Medical Center, presents scientific evidence on the mechanisms of diabetes control after surgery. Clinical studies have shown that procedures that simply restrict the stomach’s size (i.e., gastric banding) improve diabetes only by inducing massive weight loss. By studying diabetes in animals, Dr. Rubino was the first to provide scientific evidence that gastrointestinal bypass operations involving rerouting the gastrointestinal tract (i.e., gastric bypass) can cause diabetes remission independently of any weight loss, and even in subjects that are not obese. “By answering the question of how diabetes surgery works, we may be answering the question of how diabetes itself works,” says Dr. Rubino, who is a professor in the Department of Surgery at Weill Cornell Medical College and chief of gastrointestinal metabolic surgery at NewYork-Presbyterian/Weill Cornell. Dr. Rubino’s prior research has shown that the primary mechanisms by which gastrointestinal bypass procedures control diabetes specifically rely on the bypass of the upper small intestine — the duodenum and jejunum. This is a key finding that may point to the origins of diabetes. “When we bypass the duodenum and jejunum, we are bypassing what may be the source of the problem,” says Dr. Rubino, who is heading up NewYork-Presbyterian/Weill Cornell’s Diabetes Surgery Center. In fact, it has become increasingly evident that the gastrointestinal tract plays an important role in energy regulation, and that many gut hormones are involved in the regulation of sugar metabolism. “It should not surprise anyone that surgically altering the bowel’s anatomy affects the mechanisms that regulate blood sugar levels, eventually influencing diabetes,” Dr. Rubino says.
Ralph’s Note – This is not the whole article. I just wanted to illustrate the direction of diabetes research. In this case the bypassing of the small intestine, I find extreme. Due to vital nutrient absorption at those sites.
Public release date: 6-Mar-2008
When the chips are down — soak them!
Good news for chips lovers everywhere – new research in SCI’s Journal of the Science of Food and Agriculture shows that pre-soaking potatoes in water before frying can reduce levels of acrylamide.
Acrylamide is a naturally occurring chemical that occurs when starch rich foods are cooked at high temperatures, such as frying, baking, grilling or roasting.
There has been growing concern that acrylamide – found in a wide range of foods – may be harmful to health and may cause cancer in animals.
But the new research by the UK team led by Dr Rachel Burch from Leatherhead Food International found that a simple measure of pre-soaking potatoes before frying can dramatically reduce the formation of acrylamide and may therefore reduce any subsequent risk it may pose.
Dr Rachel Burch said: “There has been much research done by the food industry looking at reducing acrylamide in products but less so on foods cooked at home and we wanted to explore ways of reducing the level of acrylamide in home cooking.”
The study found that washing raw French fries, soaking them for 30 mins and soaking them for 2 hours reduced the formation of acrylamide by up to 23%, 38% and 48% respectively but only if they were fried to a lighter colour. The jury is still out on chips that are fried to a deep, dark brown.
Ralph’s Note – Good…Now they are only 52% carcinogenic.
Public release date: 6-Mar-2008
High levels of estrogen associated with breast cancer recurrence
PHILADELPHIA – Women whose breast cancer came back after treatment had almost twice as much estrogen in their blood than did women who remained cancer-free – despite treatment with anti-estrogen drugs in a majority of the women –according to researchers in a study published in the March issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.
The findings suggest that high levels of estrogen contribute to an increased risk of cancer recurrence, just as they lead to the initial development of breast cancer, said the study’s lead author, Cheryl L. Rock, Ph.D., a professor in the Department of Family and Preventive Medicine at the University of California, San Diego.
“While this makes sense, there have been only a few small studies that have looked at the link between sex hormones in the blood and cancer recurrence,” she said. “This is the largest study to date and the only one to have included women taking agents such as tamoxifen to reduce estrogen’s effect on cancer growth
What the results mean for women who have already been treated for breast cancer is that they should do as much as they can to reduce estrogen in their blood, such as exercising frequently and keeping weight down,” she added. “Taking anti-estrogen drugs like tamoxifen may not completely wipe out the hormone’s effect in women who have high levels of estrogen.”
Researchers found that higher estradiol concentrations, in all forms, significantly predicted cancer recurrence. Overall, women whose cancer came back had an average total estradiol concentration that was more than double the average for women who remained cancer-free. Increased levels of testosterone or SHBG levels were not associated with recurrence, contradicting the findings of several previous studies.
Although genetic and metabolic factors likely influence the relationship between circulating sex hormones and risk of breast cancer recurrence, Rock said the study provides solid evidence that higher concentrations of estradiol in the blood contribute to risk for breast cancer recurrence.
Public release date: 6-Mar-2008
U of I scientists aim to overcome allergic reactions to soy
URBANA – If you’re allergic to soy, help is on the way. Two University of Illinois studies show that fermenting soy dramatically reduces its potential allergenicity and also increases the number of essential amino acids in soy products, making them a healthy and a safe choice for consumers.
“When we fermented soy seeds, flour, or meal by introducing certain microorganisms, inmmunoreactivity was significantly reduced—by as much as 99 percent. This shows that we have the potential of developing nutritious, hypoallergenic soy products,” said Elvira de Mejia, a U of I associate professor of food science and human nutrition.
The scientist achieved these results when she challenged the blood plasma of persons allergic to soy with protein extracts from both fermented and unfermented soy products. Plasma samples were obtained from the World Health Organization.
“Why do we see this reduced immunoreactivity? During the fermentation process, proteins are broken down into very small pieces, pieces that can’t be identified by the antibodies that produce the allergic reaction,” de Mejia explained.
Because of soy’s health benefits, de Mejia would like to make sure soy foods can be safely eaten by all people. Soy is a source of high-quality protein, oil, B vitamins, fiber, and essential fatty acids, and it also contains phytochemicals that may help prevent chronic diseases, including heart disease, some cancers, osteoporosis, and diabetes, she said.
And, although soy allergy affects only 0.5 percent of the population, that figure may be rising. Because soy is used as in ingredient in many food products, de Mejia said that a technique that can eliminate its allergenicity is widely sought.
In the two U of I studies, which were done in collaboration with the Instituto de Fermentaciones Industriales (CSIC) in Madrid, Spain, soy was subjected to both solid and liquid fermentation by exposing samples to a number of microorganisms, including bacteria, molds, and yeast.
L. plantarum-fermented soy flour showed the highest reduction in immunoreactivity—96 to 99 percent—depending upon the sensitivity of the human plasma, the scientist said.
“Our next step will be to optimize the fermentation conditions to produce zero-tolerance allergens,” she said.
De Mejia noted that fermentation had also improved the essential amino acid composition in the soy products and produced new peptides that may be beneficial.
“We want to evaluate some of the bioactive peptides that were produced during fermentation because we believe they may have other benefits. In particular, we’re interested in their effect on lipogenesis, so we’ll be testing these hydrolysates in adipose cells,” she said.
The increase in the number of small bioactive peptides was attributed to partial digestion of large soybean peptides by enzymes secreted by the microorganisms used in fermentation, she said.
Plaimein Amnuaycheewa, a master’s degree student in de Mejia’s lab, is currently working on the allergenicity project, and Cristina Martinez-Villaluenga, a Marie Curie fellow, is working with allergenicity and adipogenesis.
Public release date: 6-Mar-2008
UCLA study finds that broccoli may help boost the aging immune system
Eat your broccoli! That’s the advice from UCLA researchers who have found that a chemical in broccoli and other cruciferous vegetables may hold a key to restoring the body’s immunity, which declines as we age.
Published in this week’s online edition of the Journal of Allergy and Clinical Immunology, the study findings show that sulforaphane, a chemical in broccoli, switches on a set of antioxidant genes and enzymes in specific immune cells, which then combat the injurious effects of molecules known as free radicals that can damage cells and lead to disease.
Free radicals are byproducts of normal body processes, such as the metabolic conversion of food into energy, and can also enter the body through small particles present in polluted air. A supercharged form of oxygen, these molecules can cause oxidative tissue damage, leading to disease — for example, triggering the inflammation process that causes clogged arteries. Oxidative damage to body tissues and organs is thought to be one of the major causes of aging.
“The mysteries of aging have always intrigued man,” said Dr. Andre Nel, the study’s principal investigator and chief of nanomedicine at the David Geffen School of Medicine at UCLA. “While we have known for some time that free radicals are important in aging, most of the past attention has focused on the mechanisms that produce free radicals rather than addressing the pathways used by the body to suppress their production.”
A dynamic equilibrium exists in the body between the mechanisms that lead to increased free radical production and those antioxidant pathways that help combat free radicals.
“Our study contributes to the growing understanding of the importance of these antioxidant defense pathways that the body uses to fight free radicals,” said Nel, a practicing clinical allergist and immunologist at the Geffen School. “Insight into these processes points to ways in which we may be able to alleviate the effects of aging.”
The delicate balance between pro-oxidant and antioxidant forces in the body could determine the outcome of many disease processes that are associated with aging, including cardiovascular disease, degenerative joint diseases and diabetes, as well as the decline in efficiency of the immune system’s ability to protect against infectious agents.
“As we age, the ability of the immune system to fight disease and infections and protect against cancer wears down as a result of the impact of oxygen radicals on the immune system,” Nel said.
According to the UCLA study, the ability of aged tissues to reinvigorate their antioxidant defense can play an important role in reversing much of the negative impact of free radicals on the immune system. However, until this current study, the extent to which antioxidant defense can impact the aging process in the immune system was not properly understood.
“Our defense against oxidative stress damage may determine at what rate we age, how it will manifest and how to interfere in those processes,” Nel said. “In particular, our study shows that a chemical present in broccoli is capable of stimulating a wide range of antioxidant defense pathways and may be able to interfere with the age-related decline in immune function.”
The UCLA team not only found that the direct administration of sulforaphane in broccoli reversed the decline in cellular immune function in old mice, but they witnessed similar results when they took individual immune cells from old mice, treated those cells with the chemical outside the body and then placed the treated cells back into a recipient animal.
In particular, the scientists discovered that dendritic cells, which introduce infectious agents and foreign substances to the immune system, were particularly effective in restoring immune function in aged animals when treated with sulforaphane.
“We found that treating older mice with sulforaphane increased the immune response to the level of younger mice,” said Hyon-Jeen Kim, first author and research scientist at the Geffen School.
To investigate how the chemical in broccoli increased the immune system’s response, the UCLA group confirmed that sulforaphane interacts with a protein called Nrf2, which serves as a master regulator of the body’s overall antioxidant response and is capable of switching on hundreds of antioxidant and rejuvenating genes and enzymes.
Nel said that the chemistry leading to activation of this gene-regulation pathway could be a platform for drug discovery and vaccine development to boost the decline of immune function in elderly people.
“This is a radical new way of thinking in how to increase the immune function of elderly people to possibly protect against viral infections and cancer,” Nel said. “We may have uncovered a new mechanism by which to boost vaccine responses by using a nutrient chemical to impact oxidant stress pathways in the immune system.”
Kim said that although there is a decline in Nrf2 activity with aging, this pathway remains accessible to chemicals like sulforaphane that are capable of restoring some of the ravages of aging by boosting antioxidant pathways.
The next step is further study to see how these findings would translate to humans.
“Dietary antioxidants have been shown to have important effects on immune function, and with further study, we may be adding broccoli and other cruciferous vegetables to that list,” Nel said.
For now, Nel suggests including these vegetables as part of a healthy diet.
Nel said that these findings offer a window into how the immune system ages.
“We may find that combating free radicals is only part of the answer. It may prove to be a more multifaceted process and interplay between pro- and antioxidant forces,” he said.
Public release date: 7-Mar-2008
One small step for man, one giant leap for advertising
The campaign to broadcast the first ever advert into space is announced as part of Doritos ‘You Make It We Play It’ initiative, launched today (Friday March 7)- with University of Leicester space scientists playing a key part in the process.
The British public is being asked to shoot a 30-second ad about what they perceive life on earth to be as part of Doritos ‘You Make It, We Play It’ user-generated-content campaign. The winning advert in the competition will be beamed past the earth’s atmosphere, beyond our solar system and into the Universe, to anyone ‘out there’ that may be watching. The winning ad will also be broadcast on terrestrial TV.
On 12th June, the space-bound ad will be broadcast from a 500MHz Ultra High Frequency Radar from the EISCAT Space Centre in Svalbard, which lies in the Arctic Ocean about midway between northern Norway and the North Pole.
The transmission is being directed at a solar system just 42 light years away from Earth with planets that orbit its star ’47 Ursae Majoris’ (UMa). 47 UMa is located in the Great Bear Constellation (also known as “The Plough”) – easily identifiable to even the most amateur stargazer. It is very similar to our Sun and is believed to host a habitable zone that could potentially harbour small terrestrial planets and support life as we know it.
Ralph’s Note- I Know it has nothing to do with health, but the irony is classic. Of all the messages we can broadcast out into space. To think our first contact with a new life form may be a Doritos commercial will be priceless.
Public release date: 7-Mar-2008
Curing addiction with cannabis medicines
Smokers trying to quit in the future could do it with the help of cannabis based medicines, according to research from The University of Nottingham.
Teams of pharmacologists, studying the cannabis-like compounds which exist naturally in our bodies (endocannabinoids), are exploring the potential for medical treatment. This includes treating conditions as diverse as obesity, diabetes, depression and addiction to substances like nicotine.
Scientists have known about endocannabinoids since the mid-1990s. This led to an explosion in the number of researchers looking into the future medical uses of cannabinoids and cannabis compounds.
Dr Steve Alexander, Associate Professor in the School of Biomedical Sciences, focused on a number of these projects in editing the first themed podcast for the British Journal of Pharmacology.
Dr Alexander said: “It is clear that there is very realistic potential for cannabinoids as medicines. Scientists are looking at a range of possible applications.”
One of these researchers is Professor David Kendall, a cellular pharmacologist at the University: “The brain is full of cannabinoid receptors. And so, not surprisingly with diseases like depression and anxiety, there’s a great deal of interest in exploiting these receptors and in doing so, developing anti-depressant compounds.”
Addiction is a real target — researchers like Professor Kendall believe the endocannabinoids could be a crucial link to addictive behaviour: “We know that the endocannabinoid system is intimately involved in reward pathways and drug seeking behaviour. So this tends to indicate that that if the link involving endocannabinoids and the reward pathway, using inhibitors, can be interrupted, it could turn down the drive to seek addictive agents like nicotine.”
Because cannabinoids have also been shown to bring down blood pressure, it is hoped that related compounds can be used in patients with conditions like hypertension.
Dr Michael Randall, a cardiovascular pharmacologist at the University has looked at how endocannabinoids cause blood vessels to relax. “This could have many implications,” Dr Randall said. “The endocannabinoids appear to lower blood pressure under certain conditions; states of shock for example. If the endocannabinoids are of physiological importance, this could have real therapeutic possibilities.”
“In terms of getting better medicines the endocannabinoid system has a lot to offer,” said Dr Alexander. “The range of cannabis-related medicines is currently limited, but by increasing our knowledge in this area we can increase our stock.”
Ralph’s Note- The first line in paragraph two is priceless. Seriously though, trading one addictive compound for another has not worked yet.(ex. Morphine, Heroin, Cocaine, Alcohol)
Public release date: 7-Mar-2008
New bacteria contaminate hairspray
Scientists in Japan have discovered a new species of bacteria that can live in hairspray, according to the results of a study published in the March issue of the International Journal of Systematic and Evolutionary Microbiology.
“Contamination of cosmetic products is rare but some products may be unable to suppress the growth of certain bacteria,” says Dr Bakir from the Japan Collection of Microorganisms, Saitama, Japan. “We discovered a new species of bacteria called Microbacterium hatanonis, which we found contaminates hairspray.”
“We also found a related species, Microbacterium oxydans in hairspray which was originally isolated from hospital material. Microbacterium species have been identified in milk, cheese, beef, eggs and even in the blood of patients with leukaemia, on catheters and in bone marrow.”
The scientists looked at the appearance and diet of the bacterium, then analysed its genome to show that it is an entirely new species. “It has been named in honour of Dr Kazunori Hatano, for his contribution to the understanding of the genus Microbacterium,” says Dr Bakir. Microbacterium hatanonis is rod-shaped and grows best at 30°C and pH neutral.
Scientists now need to determine the clinical importance of the new species, as similar bacteria have been found to infect humans. “Further testing will establish whether the species is a threat to human health,” says Dr Bakir. “We hope our study will benefit the formulation of hairspray to prevent contamination in the future.”
Public release date: 9-Mar-2008
Oregon study raises questions on synthetic progestins
The widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women in a study done at the University of Oregon. The finding, researchers said, raises concerns about long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.
The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis.
“The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems,” said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO’s human physiology department. He stressed, however, that a longer, larger study is needed.
MPA is the progestin that was used in the Women’s Health Initiative (WHI), including a clinical study on hormone-replacement therapy halted because of health concerns in postmenopausal women. MPA is the active ingredient of Provera, which is used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of the menopause.
UO researchers also found that MPA had an effect on concentrations of endothelin-1, a peptide that promotes cell division and serves as a mediator of inflammation. It also acts as a constricting factor for blood vessels. When peptide levels rise, endothelin-1 is suspected to play a key role in many diseases of the airways, pulmonary circulation, inflammatory lung diseases and vasoconstriction of blood vessels. UO researchers saw levels decline with estradiol alone, but increase substantially with the addition of MPA, negating the benefits of the estrogen.
Kaplan stressed that this project was a starting point of “major basic science research, so this study does not say women should change what they are doing.”
“We can say that we saw vascular changes in the arteries of the arm that have been shown in previous studies involving coronary arteries,” he added. “This study does let us say that whatever changes we are seeing are important not just for the arm but probably for most of the major arteries in the body, and this is important for cardiac disease.”
Public release date: 10-Mar-2008
Magnesium associated with lower risk for some strokes in male smokers
Male smokers who consume more magnesium appear to have a lower risk for cerebral infarction, a type of stroke that occurs when blood flow to the brain is blocked, according to a report in the March 10 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Recent studies indicate that changes in diet may help prevent stroke, according to background information in the article. Hypertension, or high blood pressure, is a risk factor for stroke; therefore, dietary measures that reduce blood pressure may in turn affect stroke risk. Consuming more magnesium, calcium and potassium has been associated with lower blood pressure in previous studies, while sodium has been positively associated with hypertension.
Susanna C. Larsson, Ph.D., of the Karolinska Institutet, Stockholm, Sweden, and colleagues analyzed the diets of 26,556 Finnish male smokers age 50 to 69 years who had not previously had strokes. In addition to the types of food they ate, the men reported other characteristics including medical, smoking and physical activity histories. Their height, weight and blood pressure were recorded, and a blood sample was taken.
During an average of 13.6 years of follow-up, 2,702 of the men had cerebral infarctions; 383 had intracerebral hemorrhages, which involve bleeding into the brain tissue; 196 had subarachnoid hemorrhages, or bleeding between the brain and the thin tissues that cover it; and 84 had unspecified types of strokes.
After adjusting for age and cardiovascular risk factors, such as diabetes and cholesterol level, men who consumed the most magnesium (an average of 589 milligrams per day) had a 15 percent lower risk for cerebral infarction than those who consumed the least (an average of 373 milligrams per day). The association was stronger in men younger than 60 years. Magnesium intake was not associated with a lower risk of intracerebral or subarachnoid hemorrhage, and calcium, potassium and sodium intake were not associated with risk for any type of stroke.
“An inverse association between magnesium intake and cerebral infarction is biologically plausible,” the authors write. In addition to lowering blood pressure, magnesium may influence cholesterol concentrations or the body’s use of insulin to turn glucose into energy. Either of these mechanisms would affect the risk for cerebral infarction but not hemorrhage.
The results “suggest that a high consumption of magnesium-rich foods, such as whole-grain cereals, may play a role in the prevention of cerebral infarction,” they write. “Whether magnesium supplementation lowers the risk of cerebral infarction needs to be assessed in large, long-term randomized trials.”
Ralph’s Note – Both groups had a much higher average magnesium intake, than the average U.S. citizen does. According to the US Department of Agricultures 1994 Continuing Survey of Food intakes by Individuals, the mean magnesium intake by males aged nine and older was 323 mg/day – far below today’s RDA of 420 mg/day.
Public release date: 10-Mar-2008
HPV vaccine reduces abnormal pap test results
BIRMINGHAM, Ala. – A significant drop in abnormal Pap test results happened after girls and women were given a vaccine to prevent cervical cancer, according to a researcher at the University of Alabama at Birmingham (UAB).
The findings show the vaccine, named GARDASIL, appears to prevent the development of cell changes that lead to cervical disease, the researcher said.
In testing GARDASIL reduced abnormal Pap test results by 43 percent compared to women not given the vaccine. The 43 percent reduction was for tests that found pre-cancerous changes called high-grade squamous intraepithelial lesions (HSIL) more than three years after women were given the vaccine.
GARDASIL reduced other abnormal Pap results, including milder pre-malignant cell changes, by 16 to 35 percent compared to women not given the vaccine.
While the findings are not definitive that GARDASIL prevents cancer, they do signal the vaccine will spare thousands of women a diagnosis of cell abnormality or malignant changes that may lead to more tests and possibly surgery, said Warner Huh, M.D., associate professor in the UAB Division of Gynecologic Oncology and the doctor chosen to present the data.
“Clearly the vaccine’s benefits include something that can be appreciated by women and daughters fairly quickly,” Huh said. “This is a positive first sign, and it will take many more years to know definitively if the vaccine prevents cancer.”
For many unvaccinated women HPV infections clear up naturally without causing any cervical problems, as do many pre-malignant lesions. In other cases, HPV prompts cell changes that can gradually put women at greater risk of cervical cancer.
Nearly 25 million U.S. women between the ages of 14 and 59 are infected with HPV, and the annual cost of screening and treating cervical abnormalities is about $4 billion, according to a statement from the Society of Gynecologic Oncologists. “Dr. Huh’s study concludes that the trials covered in this paper indicate an overall benefit of vaccination,” the society’s statement said.
Ralph’s Note- So does it prevent cancer, or not ?
Public release date: 10-Mar-2008
Mayo Clinic proceedings highlights research about cardiovascular benefits of omega-3 fatty acids
ROCHESTER, Minn. — Thousands of research studies have documented how the oils known as omega-3 fatty acids can benefit the cardiovascular system, particularly among people diagnosed with coronary artery disease. The incredible volume of research on this topic creates difficulty for many physicians and patients to stay current with findings and recommendations related to these oils. In the March issue of Mayo Clinic Proceedings, contributors briefly summarize current scientific data on omega-3 fatty acids and cardiovascular health, focusing on who benefits most from their protective effects, recommended guidelines for administration and dosing, and possible adverse effects associated with their use.
Two omega-3 fatty acids that have been associated with cardiovascular benefit, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are found in fish oils. The best source for DHA and EPA are fatty coldwater fish such as herring, mackerel, salmon and tuna. Fish oil supplements or algae supplements also can provide omega-3 fatty acids.
Author James O’Keefe, M.D., a cardiologist from the Mid America Heart Institute in Kansas City, Mo., cites the results of several large trials that demonstrated the positive benefits associated with omega-3 fatty acids, either from oily fish or fish oil capsules.
“The most compelling evidence for the cardiovascular benefit provided by omega-3 fatty acids comes from three large controlled trials of 32,000 participants randomized to receive omega-3 fatty acid supplements containing DHA and EPA or to act as controls,” explains Dr. O’Keefe. “These trials showed reductions in cardiovascular events of 19 percent to 45 percent. Overall, these findings suggest that intake of omega-3 fatty acids, whether from dietary sources or fish oil supplements, should be increased, especially in those with or at risk for coronary artery disease.”
How much fish oil should people attempt to incorporate into their diets” According to Dr. O’Keefe, people with known coronary artery disease should consume about 1 gram per day, while people without disease should consume at least 500 milligrams (mg) per day.
“Patients with high triglyceride levels can benefit from treatment with 3 to 4 grams daily of DHA and EPA,” says Dr. O’Keefe. “Research shows that this dosage lowers triglyceride levels by 20 to 50 percent.”
About two meals of oily fish can provide 400 to 500 mg of DHA and EPA, so patients who need to consume higher levels of these fatty-acids may choose to use fish oil supplements to reach these targets.
Dr. O’Keefe also notes that research supports the effectiveness of combining the consumption of fish oil with the use of cholesterol-lowering medications called statins. Combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular health beyond the benefits provided by statin therapy alone. Blood DHA and EPA levels could one day be used to identify patients with deficient levels and to individualize therapeutic recommendations.
Dr. O’Keefe found little evidence of serious adverse effects associated with fish oil consumption. “In prospective placebo-controlled trials, no adverse effects were observed to occur at a frequency of more than 5 percent, and no difference in frequency was noted between the placebo and omega-3 fatty acid groups,” he says.
The most commonly observed side effects include nausea, upset stomach and a “fishy burp.” Taking the supplement at bedtime or with meals, keeping fish oil capsules in the freezer or using enteric-coated supplements may help reduce burping and upset stomach symptoms.
Public release date: 11-Mar-2008
Postoperative chemotherapy does not improve survival in gastric cancer patients
The use of combination chemotherapy following surgery did not improve survival in patients with gastric cancer, according to a randomized clinical trial published online March 11 in the Journal of the National Cancer Institute.
The only potentially curative therapy currently available for non-metastatic gastric cancer is surgery. Recent studies have suggested that a combination of cisplatin, epirubicin, 5-fluorouracil and leucovorin (PELF) improves outcome in patients with metastatic gastric cancer.
To test the PELF combination in patients with localized disease, Francesco Di Costanzo, M.D., of the University Hospital Careggi in Florence, Italy, and colleagues in the Italian Oncology Group for Cancer Research conducted a randomized controlled trial in which 258 patients were treated with surgery or surgery followed by chemotherapy.
With a median follow-up of 72.8 months, there was no significant difference in disease-free survival or overall survival between the two trial arms. Specifically, 47.7 percent of the patients treated with chemotherapy had progressive disease compared with 51.6 percent of patients in the control arm. Overall survival was similar; at the end of the follow-up period, 47 percent of the patients in the chemotherapy were still alive compared with 45.3 percent in the surgery-only arm.
“Our study confirms that a dose-intense regimen like PELF, which showed very promising results in advanced gastric cancer, is not effective in an adjuvant setting,” the authors write. Considering the negative results in this trial and other recent adjuvant chemotherapy trials in gastric cancer, the authors write, “Adjuvant chemotherapy alone remains a controversial approach in operable gastric cancer.”
In an accompanying editorial, Aiwen Wu, M.D., and Jiafu Ji, M.D., of the Beijing Cancer Hospital and Institute in China discuss the conflicting results obtained from recent trials that tested the value of chemotherapy and radiation in localized gastric cancer.
Despite the inconsistency of the overall data, the editorialists conclude that chemotherapy, radiation, or a combination of the two should be used in patients with gastric cancer. “Surgery alone is no longer the standard treatment for patients with resectable gastric cancer, independent of the patient population or the practice location,” they write.
Public release date: 11-Mar-2008
Weight loss more effective than intensive insulin therapy for type 2 diabetics
DALLAS – March 11, 2008 – Weight-loss and major lifestyle changes may be more effective than intensive insulin therapy for overweight patients with poorly controlled, insulin-resistant type 2 diabetes, according to a diabetes researcher at UT Southwestern Medical Center.
The National Heart, Lung, and Blood Institute of the National Institutes of Health recently halted part of an ongoing clinical trial on diabetes and heart disease after more than 250 people died while receiving intense treatment to drive their blood glucose levels below current clinical guidelines.
The evidence is compelling that when insulin levels are high, certain tissues are overloaded with fatty molecules, which leads to insulin resistance. And yet, the high blood glucose levels of many obese patients with insulin-resistant type 2 diabetes are being treated with increasing amounts of insulin in an attempt to overpower that resistance. While high doses of insulin may lower glucose levels, it will also increase the fatty molecules and may cause organ damage.
In a commentary in the March 12 issue of The Journal of the American Medical Association, Dr. Roger Unger, professor of internal medicine, wrote about the recent findings of his own and other labs that link insulin resistance to excess accumulation of fatty molecules in liver and muscle.
Dr. Unger, who has investigated diabetes, obesity and insulin resistance for more than 50 years said intensive insulin therapy is contraindicated for obese patients with insulin-resistant type 2 diabetes because it increases the fatty acids that cause diabetes. Instead, the most rational therapy eliminates excess calories, thereby reducing the amount of insulin in the blood and the synthesis of the fatty acids stimulated by the high insulin. Giving more insulin simply increases body fat.
“Evolution was unprepared for the change in the American diet to processed fast food and drive-through lanes,” he said. “There’s no way that our genes could evolve to gird themselves against the superabundance of very, very high-calorie foods that have flooded the U.S.”
Before the discovery of insulin, starvation was the only treatment for diabetes, said Dr. Unger, who is a member of the National Academy of Sciences.
“Today there are many treatment options, including bariatric surgery, if necessary, to lower the fat content in the body before you start giving insulin,” he said. “The fat is causing insulin resistance and killing the insulin-producing beta cells in the pancreas – that is what is causing type 2 diabetes.”
Giving more insulin simply channels the glucose into fat production. There is now a spectrum of therapies that improve diabetes by correcting the insulin resistance by reducing the body fat. Insulin treatment would be indicated only if all these fail.
Dr. Unger said insulin should be given to patients with insulin deficiency, but not if the insulin levels are already very high but ineffective. “Giving more insulin to an insulin-resistant patient is akin to raising the blood pressure of a patient with high blood pressure to overcome resistance to blood flow. Instead, you would try to reduce the resistance,” he said.
In the commentary, Dr. Unger said the increase in the number of patients with insulin-resistant type 2 diabetes can be traced to the epidemic of obesity that began in the U.S. after World War II, when food preparation was moved from the family kitchen to factories and companies that produce high-fat, calorie-dense foods, leading both men and women to consume substantially more calories on a daily basis. In addition, technological advancements such as televisions, computers and automobiles reduced the number of calories burned per day.
Type 2 diabetes occurs when the body is unable to make enough of the hormone insulin to compensate for insulin resistance. The condition affects between 18 million and 20 million people in the U.S.
Factors that increase the risk of type 2 diabetes include obesity, age and lack of exercise. Over a period of years, high blood sugar damages nerves and blood vessels, leading to complications such as heart disease, stroke, blindness and kidney disease.
Public release date: 12-Mar-2008
Study raises caution on new painkillers
A new class of painkillers that block a receptor called TRPV1 may interfere with brain functions such as learning and memory, a new study suggests. The experiments with rat brain found that the TRPV1 receptor regulates a neural mechanism called long-term depression, which is believed to be central to establishing memory pathways in the brain.
The researchers said their findings also suggest that the function of TRPV1 in neural tissue may explain reported side effects of the anti-obesity drug Acomplia, widely used outside the U.S. While Acomplia has been approved in Europe, the FDA denied U.S. approval because of concerns that the drug increases risk of depression and suicide. The researchers, led by Julie Kauer, published their findings in the March 13, 2008, issue of the journal Neuron, published by Cell Press.
TRPV1, or “transient receptor potential vanilloid 1,” is a pain receptor whose activation causes the pain in inflammation. The receptor is also triggered by noxious chemicals such as the chili pepper compound capsaicin.
Drug companies have been testing TRPV1 receptor blockers to treat the pain of inflammation and nerve damage in the peripheral nervous system (PNS). However, besides being expressed in the PNS, TRPV1 is expressed in areas of the central nervous system (CNS), including the hippocampus, the brain’s learning center. However, its function in the brain was not well established.
In their experiments with rat brain slices, Kauer and colleagues explored whether TRPV1 plays a role in long-term depression (LTD), which is a weakening of the signaling between neurons that takes place at the connections called synapses. LTD, and the counterpart strengthening of connections, called long-term potentiation, are key to the formation of neural pathways in learning, a process called plasticity.
The researchers found that they could block LTD in the brain slices using drugs that block TRPV1. Also, they could induce LTD using the TRPV1-activating compound capsaicin.
What’s more, they found that genetically knocking out the TRPV1 receptor in mice drastically reduced LTD in the animals.
“In this study, we show for the first time that TRPV1 receptors are necessary and sufficient for a novel form of long-term depression at excitatory synapses,” concluded the researchers. “The broad distribution of TRPV1 receptors in the brain suggests that these receptors could play a similar role in synaptic plasticity throughout the CNS.”
The researchers said their findings suggest that drugs targeting TRPV1 could act not only on pain receptors in the PNS, but in the brain as well. They also wrote that their findings and those of other researchers “indicate that drugs that bind to CNS TRPV1 receptors are likely to influence more than just pain-related functions.”
“Further work will help to ascertain whether hippocampal TRPV1 receptors could provide novel drug targets for neurological disorders,” they wrote.
What’s more, they concluded that their findings suggest a mechanism for the reported side effects of the anti-obesity drug Acomplia.
“A large percentage of patients stop taking this drug as a result of psychiatric side effects, and our findings suggest the possibility that some of the central effects of [Acomplia] result from the antagonism of TRPV1 receptors …,” they wrote.
“The results from this study have important implications for the development of drugs targeting TRPV1,” wrote Benedict Alter and Robert Gereau in a preview of the paper in the same issue of Neuron. They wrote that the Kauer study as well as others indicating widespread expression of the TRPV1 receptor, “cloud the prospects of TRPV1-targeted analgesics. If TRPV1 is important in hippocampal synaptic plasticity, as this study suggests, then systemic TRPV1 antagonists may interfere with many processes thought to rely on hippocampal synaptic plasticity, such as learning and memory.”
However, wrote Alter and Gereau, “there is a silver lining to this cloud.” Drugs targeting TRPV1 in both the peripheral and pain-processing regions of the central nervous system “actually produced greater analgesia than antagonists thought to primarily act in the periphery.” Also, they noted, targeting TRPV1 may be useful in treating other neural disorders, such as epilepsy.
“Regardless of the uncertain future of TRPV1-targeted therapeutics,” they wrote, such studies “are important not only for drug development but also for expanding our knowledge of synaptic function.”
Public release date: 12-Mar-2008
Is a cup of tea really the answer to everything — even anthrax?
A cup of black tea could be the next line of defense in the threat of bio-terrorism according to new international research
A cup of black tea could be the next line of defence in the threat of bio-terrorism according to new international research.
A new study by an international team of researchers from Cardiff University and University of Maryland has revealed how the humble cup of tea could well be an antidote to Bacillus anthracis –more commonly know as anthrax.
As a nation, Brits currently drink 165 million cups of tea, and the healing benefits of the nation’s favourite beverage have long been acknowledged.
But now the team of scientists led by Professor Les Baillie from Welsh School of Pharmacy at Cardiff University and Doctor Theresa Gallagher, Biodefense Institute, part of the Medical Biotechnology Centre of the University of Maryland Biotechnology Institute in Baltimore, has found that the widely-available English Breakfast tea has the potential to inhibit the activity of anthrax, as long as it is black tea.
Anthrax – a potentially fatal human disease – is caused by the bacterium Bacillus anthracis. A very serious and rapidly progressing form of the disease occurs when bacterial spores are inhaled making anthrax a potent threat when used as a biological warfare agent.
Published in the March issue of the Society for Applied Microbiology’s journal Microbiologist, Professor Baillie said: “Our research sought to determine if English Breakfast tea was more effective than a commercially available American medium roast coffee at killing anthrax. We found that special components in tea such as polyphenols have the ability to inhibit the activity of anthrax quite considerably.”
The study provides further evidence of the wide range of beneficial physiological and pharmalogical effects of this common household item.
The research also shows that the addition of whole milk to a standard cup of tea completely inhibited its antibacterial activity against anthrax.
Professor Baillie continued: “I would suggest that in the event that we are faced with a potential bio-terror attack, individuals may want to forgo their dash of milk at least until the situation is under control.
“What’s more, given the ability of tea to bring solace and steady the mind, and to inactivate Bacillus anthracis and its toxin, perhaps the Boston Tea Party was not such a good idea after all.”
Public release date: 12-Mar-2008
Killer fungus spells disaster for wheat
A WHEAT disease that could destroy most of the world’s main wheat crops could strike south Asia’s vast wheat fields two years earlier than research had suggested, leaving millions to starve. The fungus, called Ug99, has spread from Africa to Iran, and may already be in Pakistan. If so, this is extremely bad news, as Pakistan is not only critically reliant on its wheat crop, it is also the gateway to the Asian breadbasket, including the vital Punjab region.
Scientists met this week in Syria to decide on emergency measures to track Ug99’s progress. They hope to slow its spread by spraying fungicide or even stopping farmers from planting wheat in the spores’ path. The only real remedy will be new wheat varieties that resist Ug99, and they may not be ready for five years. The fungus has just pulled ahead in the race.
Ug99, a virulent strain of black stem rust (Puccinia graminis) was identified in Uganda in 1999. Since then it has invaded Kenya and Ethiopia and, last year, Yemen. From previous fungal invasions, scientists expected the prevailing winds to carry Ug99 spores to Egypt, Turkey and Syria, and then east to Iran, a major wheat-grower, buying them some time. But on 8 June 2007, Cyclone Gonu hit the Arabian peninsula, the worst storm there for 30 years.
“We know it changed the winds,” says Wafa Khoury of the UN Food and Agriculture Organization in Rome, because desert locusts the FAO had been tracking in Yemen blew north towards Iran instead of northwest as expected. “We think it may have done that to the rust spores.” This means, she says, that Ug99 has reached Iran a year or two earlier than predicted. The fear is that the same winds could have blown the spores into Pakistan, which is also north of Yemen, and where surveillance of the fungus is limited.
There could be more unpleasant surprises in store. On mature wheat, the fungus reproduces asexually to release billions of identical spores. If the spores drift onto a barberry bush (Berberis vulgaris), however, they switch to sexual reproduction, and so could swap genes with other stem rusts to produce completely new variants. Iran is a hotspot for barberry.
Scientists have now found out how Ug99 took hold, says Rick Ward of CIMMYT, the wheat breeding institute in Mexico that started the Green Revolution. “It turns out most of Kenya was planted with a wheat variety that contained only one gene for rust resistance, SR24,” he told New Scientist.
“We advise at least two resistance genes,” says Ward. Wheat with the SR24 gene alone gives any Ug99 strains resistant to SR24 a huge advantage, just as misuse of antibiotics selects for antibiotic-resistant bacteria, says Ward. Farmers then switched to using wheat with other resistance genes and the same thing happened.
Ug99 is now resistant to the three major anti-rust genes used in nearly all the world’s wheat. “The real solution is disease resistance that relies on a number of genes,” says Ward. Wheat with multigene resistance does not so much destroy the fungus as slow it down. The hope is that with several genes involved it will be much harder for the fungus to become resistant and there will be less selection pressure for it to do so.
A breeding programme by CIMMYT and others has now uncovered some wheat types which “show promise” in tests against Ug99 in Kenya and Ethiopia, says Ronnie Coffman of Cornell University in Ithaca, New York, who chairs the programme. Funding has increased, as rich countries such as Canada and the US worry that Ug99 could hit their breadbaskets, accidentally or deliberately.
Without such fears, says Khouri, “it is hard to convince donors to take preventive actions, when people are not starving now”. But that may not be far off. “People will start starving if Ug99 cuts harvests enough to push up grain prices,” warns Ward.
The problem is that crop breeding is slow. It usually takes at least five years to cross disease-resistant lines with wheat varieties adapted to local conditions in the world’s wheat-growing countries, then grow enough seed to plant fields threatened by Ug99.
New Scientist has learned that China started a crash programme to breed resistance into Chinese wheat varieties last year, after an article on Ug99 in this magazine was translated into Chinese and circulated to top agriculture officials.
Public release date: 12-Mar-2008
Fertility in developing countries: words into action
For almost 30 years – since the world’s first “test-tube” baby was born in July 1978 – the benefits of modern infertility treatments have been largely confined to couples in developed countries. There, we have seen more than 3 million babies born as a result of IVF and, in some countries, as many as 4 per cent of all babies born conceived by modern fertility techniques.
The plight of couples in developing countries, especially women, has been acknowledged, but rarely advanced from words into action. Now, a task force of ESHRE (the European Society of Human Reproduction and Embryology), the world’s leading professional organisation in reproductive medicine, has devised a programme of fertility treatment for developing countries which aims to integrate fertility clinics within broader family health services. Two pilot IVF services have already opened in Africa.
According to Professor Oluwole Akande from University College Hospital in Ibadan, Nigeria, infertility in developing countries raises complex problems beyond those known to developed nations. “In poor resource areas,” he says, “the need for infertility treatment in general, and IVF in particular, is great. The inability to have children can create enormous problems, particularly for the woman. She might be disinherited, ostracised, accused of witchcraft, abused by local healers, separated from her spouse, or abandoned to a second-class life in a polygamous marriage.”
There are many reasons why infertility treatment has not been widely introduced in developing countries. The main explanations are poverty and limited health resources, but there is also the paradox that most of the countries where needs are greatest are also the countries where population growth is running out of control.
Says Dr Willem Ombelet, from the Genk Institute for Fertility Technology in Genk, Belgium, and co-ordinator of the ESHRE task force: “It is for these reasons that the ESHRE task force plans are to integrate infertility treatment within existing family planning and mother-care services. The most important goal is to provide treatment which is safe, affordable and culturally acceptable.
The ESHRE programme proposes three levels of treatment, but its cornerstone is the provision of affordable IVF. Currently, one cycle of IVF treatment in Europe or the USA costs between US$ 5000 and 10,000. A system of low-cost IVF now being pilot-studied in Khartoum and Cape Town aims to provide one cycle of IVF for less than $200.
One of the instigators of the low-cost IVF scheme, Dr. Luca Gianaroli from the SISMER Reproductive Medicine Unit, in Bologna, Italy, says: “It’s a different approach to IVF. We will not be able to treat every type of infertility, but many women with tubal damage as a result of infection can be helped.” While the scheme has limited laboratory facilities for incubation, embryo selection and embryo freezing, Gianaroli says triplets and high-order pregnancies will be avoided.
The cornerstones in the treatment of infertility in low-resource settings, says Ombelet, are the simplification of techniques, minimizing of complications, training for healthcare workers, and the incorporation of fertility treatments into existing healthcare programmes.
Ralph’s Note- Interesting scenario….
Extra vitamin D in early childhood cuts adult diabetes risk
Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis
Vitamin D supplements in early childhood may ward off the development of type 1 diabetes in later life, reveals a research review published ahead of print in the Archives of Disease in Childhood.
Type 1 diabetes is an autoimmune disorder, in which insulin producing beta cells in the pancreas are destroyed by the body’s own immune system, starting in early infancy. The disease is most common among people of European descent, with around 2 million Europeans and North Americans affected.
Its incidence is rising at roughly 3% a year, and it is estimated that new cases will have risen 40% between 2000 and 2010.
A trawl of published evidence on vitamin D supplementation in children produced five suitable studies, the pooled data from which were re-analysed.
The results showed that children given additional vitamin D were around 30% less likely to develop type 1 diabetes compared with those not given the supplement.
And the higher and the more regular the dose, the lower was the likelihood of developing the disease, the evidence suggested.
Levels of vitamin D, and sunlight, from which the body manufactures the vitamin, have been implicated in the risks of developing various autoimmune disorders, including multiple sclerosis and rheumatoid arthritis.
And there is a striking difference in the incidence of type 1 diabetes according to latitude and levels of sunlight exposure, with a child in Finland 400 times more likely to develop the disease than a child in Venezuela, say the authors.
Further evidence of vitamin D’s role comes from the fact that pancreatic beta cells and immune cells carry receptors or docking bays for the active forms of the vitamin.
Public release date: 13-Mar-2008
Rodent study finds artificial butter chemical harmful to lungs
A new study shows that exposure to a chemical called diacetyl, a component of artificial butter flavoring, can be harmful to the nose and airways of mice. Scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, conducted the study because diacetyl has been implicated in causing obliterative bronchiolitis (OB) in humans. OB is a debilitating but rare lung disease, which has been detected recently in workers who inhale significant concentrations of the flavoring in microwave popcorn packaging plants.
When laboratory mice inhaled diacetyl vapors for three months, they developed lymphocytic bronchiolitis – a potential precursor of OB. None of the mice, however, were diagnosed with OB.
“This is one of the first studies to evaluate the respiratory toxicity of diacetyl at levels relevant to human health. Mice were exposed to diacetyl at concentrations and durations comparable to what may be inhaled at some microwave popcorn packaging plants,” said Daniel L. Morgan, Ph.D., head of the Respiratory Toxicology Group at the NIEHS and co-author on the paper that appears online in the journal, Toxicological Sciences. The study was done in collaboration with Duke University researchers.
The authors conclude that these findings suggest that workplace exposure to diacetyl contributes to the development of OB in humans, but more research is needed.
Although exposure of laboratory animals by inhalation closely duplicates the way humans are exposed to airborne toxicants, the study points out that some anatomical differences between the mice and humans may account for why the nasal cavity of mice is more susceptible to reactive vapors than that of humans. Another reason may be that mice breathe exclusively through their noses.
The researchers also speculate that the extensive reaction of diacetyl vapors in the nose and upper airways of mice may have prevented toxic concentrations from penetrating deeper in the lung to the bronchioles or tiny airways where obstruction occurs in humans.
When the mice were exposed to high concentrations of diacetyl using a method that bypasses the nose, the researchers found lesions partially obstructing the small airways. More studies are under way to determine if these lesions progress to OB in mice.
The National Toxicology Program, headquartered at the NIEHS, plans to do a larger set of studies to provide inhalation toxicity data on artificial butter flavoring and the two major components, diacetyl and another compound called acetoin. The NTP studies will help pinpoint more definitively the toxic components of artificial butter flavoring and potentially help identify biomarkers for early detection. The NTP data will then be shared with public health and regulatory agencies so they can set safe exposure levels for these compounds and develop guidance to protect the health of workers in occupations where these chemicals are used.
Public release date: 13-Mar-2008
Study in Circulation Research details how diabetes drives atherosclerosis
Researchers have discovered how diabetes, by driving inflammation and slowing blood flow, dramatically accelerates atherosclerosis, according to research to be published in the March 14 edition of the journal Circulation Research.
Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body’s immune system to fatty build-up, more than the build-up itself, creates heart attack risk. Immune cells traveling with the blood mistake fatty deposits for intruders, akin to bacteria, home in on them, and attack. This causes inflammation that makes plaques more likely to swell, rupture and cut off blood flow.
Making matters worse, nearly 21 million Americans have diabetes, a disease where patients’ cells cannot efficiently take in dietary sugar, causing it to build up in the blood. In part because diabetes increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke.
Past work has shown that high blood sugar has two effects on cells lining blood vessels as part of atheroslerosis. First, it increases the production of free radicals, highly reactive molecules that tear about sensitive cell components like DNA, causing premature cell death (apoptosis). This process also reduces the availability of nitric oxide (NO), which would otherwise enable blood vessels to relax and blood flow to increase. In contrast to diabetes, exercise and good diet bring about faster blood flow through blood vessels. The force created by fast, steady blood flow as it drags along blood vessel walls has been shown by recent studies to protect arteries from atherosclerosis. Physical force has emerged recently as a key player in bodily function, capable of kicking off biochemical processes (e.g. weightlifting thickens bone).
“Inflammation is blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse,” said Jun-ichi Abe, M.D., Ph.D., associate professor with the Aab Cardiovascular Research Center at the University of Rochester Medical Center, and a study author. “Our study argues that a pathway surrounding a key signaling enzyme both protects the heart in normal cases, and is sabotaged by the chemicals produced in diabetes. We believe we have found a new therapeutic target for the treatment of diabetes-related damage to blood vessels.”
Public release date: 14-Mar-2008
Legal exposure to asbestos-like material linked to lung damage 25 years later
Men and women who worked in a plant that processed vermiculite tainted with asbestos-like fibers that originated from a mine in Libby, Montana, show high prevalence of scarring and thickening of the membrane that lines the chest wall some 25 years after the plant stopped using the material—even those who were exposed at or below current legal levels.
Vermiculite is a mineral that expands to nearly 20 times its original size when rapidly heated and has a number of consumer applications, from gardening products to loose-fill home insulation. The “Libby vermiculite” was first suspected of causing lung damage in the late 1970s, when researchers documented a cluster of bloody pleural effusions among workers who handled it. At one time, the Libby mine produced up to 80 percent of the vermiculite used around the world.
In 1980, researchers examined 513 individuals who worked at a plant that processed Libby vermiculite and found pleural changes or interstitial fibrosis in 2.2 percent of the overall cohort. In this follow-up study, a research team led by James Lockey, M.D., the principal investigator of the 1980 report, found that the unadjusted prevalence in the still-living members of the original cohort was 28.7 percent for pleural changes and 2.9 percent for interstitial fibrosis.
The findings are published in the second issue for March of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
The high prevalence surprised even Dr. Lockey, senior researcher at the University of Cincinnati. “I expected to see a higher rate of x-ray changes, but was surprised at the percentage,” he said. “We found that even low levels of exposure to asbestos-like fibers can cause thickening of the membrane that lines the chest wall.”
Of the 431 workers from the original group who were still living, 280 participated in the follow-up study and were interviewed about their lung health and work history, including particular exposure level and the numbers of years they worked. They were then given chest x-rays, which were assessed for pleural plaques, thickening and interstitial changes by professional radiologists.
When the researchers analyzed the workers with pleural changes by exposure levels, they found a significant trend of increasing changes with increased exposure. Workers with highest exposure levels had an average of 6 to 16 times the risk of pleural changes when compared to those who were minimally exposed. Moreover, the changes were significant even at levels of exposure currently permitted by law.
The findings indicate that “a significant number of workers exposed at the current limit would experience pleural abnormalities,” wrote Gregory Wagner, M.D., of the National Institute for Occupational Safety and Health, in an accompanying editorial.
Furthermore, regulations governing legal exposure limits to hazardous materials apply only to specific fibers, not to all types of fibers that have similar and predictable biological effects.
“When humans are exposed to any mineral fibers that are long, thin and durable in human tissue and can reach the pleural membrane, these fibers can cause health problems,” said Dr. Lockey. “Six types of asbestos are currently regulated, but other existing types of fibers that share similar characteristics are not.”
Public release date: 14-Mar-2008
Soy compound may halt spread of prostate cancer
PHILADELPHIA – A compound found in soybeans almost completely prevented the spread of human prostate cancer in mice, according to a study published in the March 15 issue of Cancer Research, a journal of the American Association for Cancer Research.
Researchers say that the amount of the chemical, an antioxidant known as genistein, used in the experiments was no higher than what a human would eat in a soybean-rich diet.
Investigators from Northwestern University found that genistein decreased metastasis of prostate cancer to the lungs by 96 percent compared with mice that did not eat the compound in their chow – making the study the first to demonstrate genistein can stop prostate cancer metastasis in a living organism.
“These impressive results give us hope that genistein might show some effect in preventing the spread of prostate cancer in patients,” said the study’s senior investigator, Raymond C. Bergan, MD, director of experimental therapeutics for the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
“Diet can affect cancer and it doesn’t do it by magic,” Bergan said. “Certain chemicals have beneficial effects and now we have all the preclinical studies we need to suggest genistein might be a very promising chemopreventive drug.”
Bergan and his team have previously demonstrated in prostate cancer cell cultures that genistein inhibits detachment of cancer cells from a primary prostate tumor and represses cell invasion. It does this by blocking activation of p38 MAP kinases, molecules which regulate pathways that activate proteins that loosen cancer cells from their tight hold within a tumor, pushing them to migrate. “In culture, you can actually see that when genistein is introduced, cells flatten themselves in order to spread out and stick strongly to nearby cells,” he said.
Public release date: 17-Mar-2008
An anti-inflammatory response to the vegan diet
Rheumatoid arthritis (RA) patients who eat a gluten-free vegan diet could be better protected against heart attacks and stroke. RA is a major risk factor for these cardiovascular diseases, but a gluten-free vegan diet was shown to lower cholesterol, low-density lipoprotein (LDL) and oxidizedLDL (OxLDL), as well as raising the levels of natural antibodies against the damaging compounds in the body that cause symptoms of the chronic inflammatory disease rheumatoid arthritis, such as phosphorylcholine. These findings are reported today in the open access journal Arthritis Research & Therapy.
The idea that we can influence our health by changing our eating habits has become a fashionable idea among lifestyle and consumer magazines. There is evidence that dietary changes can bring about health benefits but specific results are not widespread.
Now, Johan Frostegard of the Rheumatology Unit at the Karolinska University Hospital in Stockholm and colleagues divided sixty-six RA patients randomly into two groups. They randomly assigned 38 of the volunteers to eat a gluten-free vegan diet, and the other 28 a well-balanced but non-vegan diet for one year. They analysed the levels of fatty, lipid molecules in blood samples using routine analytical methods at regular periods. They also measured oxLDL and anti-phosphorylcholine (antiPC) factor at the beginning of the experiment, at 3 months and again at 12 months.
The researchers found that the gluten-free vegan diet not only reduced LDL and oxLDL levels and raised antiPC antibodies but lowered the body-mass index (BMI) of the volunteers in that group. Levels of other fatty molecules, including triglycerides and high-density lipoprotein (HDL) stayed the same. In contrast, none of the indicators differed significantly for the control groups on the conventional healthy diet.
AntiPC antibodies are studied within CVDIMMUNE, an European consortium led by Dr Frostegard with the hypothesis that such antibodies can protect against cardiovascular disease and can be used as diagnostic and therapeutic factors.
Frostegard and colleagues have now shown that diet could be used to improve the long-term health of people with rheumatoid arthritis. They concede that a bigger study group will be needed to discern which particular aspects of the diet help the most.
Public release date: 17-Mar-2008
Foodborne outbreaks from leafy greens on rise
Over the past 35 years the proportion of foodborne outbreaks linked to the consumption of leafy green vegetables has substantially increased and that increase can not be completely attributed to Americans eating more salads according to research presented today (March 17) at the 2008 International Conference on Emerging Infectious Diseases in Atlanta, Georgia.
“Consumption of leafy greens has increased over the years, but it does not completely explain the increase in the proportion of foodborne outbreaks due to leafy green consumption,” says Michael Lynch of the Centers for Disease Control and Prevention (CDC), a researcher on the study.
Prompted by the high profile E. coli outbreaks associated with spinach and lettuce in 2006, Lynch and his colleagues decided to investigate the incidence of foodborne disease outbreaks associated with leafy greens in the past. Using data from the CDC foodborne disease outbreak surveillance system they analyzed over 10,000 foodborne disease outbreaks reported between 1973 and 2006.
For the entire period, approximately 5% of all foodborne outbreaks were linked to leafy greens. Most of these (60%) were caused by norovirus, but some were caused by salmonella (10%) and E. coli (9%).
“Given recent experiences that was not a total surprise. What was interesting was when we compared the numbers to consumption data,” says Lynch.
Using per capita availability of leafy greens in the United States as a proxy for leafy green consumption, the researchers compared per capita consumption of leafy greens with the proportion of foodborne outbreaks caused by leafy green consumption.
“During the 1986-1995 period U.S. leafy green consumption increased 17% from the previous decade. During the same period, the proportion of all foodborne disease outbreaks due to leafy greens increased 60%. Likewise during 1996-2005 leafy green consumption increased 9% and leafy green-associated outbreaks increased 39%,” says Lynch.
Further investigation is necessary in order to determine other factors that may help explain the increase, says Lynch. While many foodborne outbreaks can be traced to a problem in food preparation, he notes that some outbreaks are fairly widespread, suggesting that contamination took place early in the production process, either on the farm or the processing plant.
“The proportion of outbreaks due to leafy greens has increased beyond what can be explained by increased consumption. Contamination can occur anywhere along the chain from the farm to the table. Efforts by local, state and federal agencies to control leafy green outbreaks should span from the point of harvest to the point of preparation,” says Lynch
Public release date: 17-Mar-2008
Solving the drug price crisis
The mounting U.S. drug price crisis can be contained and eventually reversed by separating drug discovery from drug marketing and by establishing a non-profit company to oversee funding for new medicines, according to two MIT experts on the pharmaceutical industry.
Stan Finkelstein, M.D., senior research scientist in MIT’s Engineering Systems Division, and Peter Temin, Elisha Gray II Professor of Economics, present their research and detail their proposal in their new book, “Reasonable Rx: Solving the Drug Price Crisis,” published by Financial Times Press.
Finkelstein and Temin address immediate national problems–the rising cost of available medicines, the high cost of innovation and the ‘blockbuster’ method of selecting drugs for development–and predict worsening new ones, unless bold steps are taken.
“Drug prices in the United States are higher than anywhere else in the world. Right now, the revenues from those drugs finance research and development of new drugs. We propose to reduce prices, not at the expense of innovation, but by changing the way innovation is financed,” said Temin, also the author of “Taking Your Medicine: Drug Regulation in the US.”
“Nationally, if we keep the current structure, in 50 years only hedge fund managers will be able to afford prescription drugs. Drug development will focus on therapies for those small groups of people who can pay a thousand dollars a pill. With income distribution widening and insurance carriers already refusing some coverage, this would be a disaster,” said Temin.
“Prescription drugs have been left out of previous efforts to reform the delivery of health care. New initiatives to expand coverage must include a plan to reduce the high cost of drugs,” Finkelstein added.
The book, which draws on the researchers’ expertise in the realms of medicine and economics, proposes eliminating the linkage between drug prices and the cost of drug discovery while financing innovation and addressing the needs of society.
Their first bold step is conceptual, recognizing that we all have a critical stake in the products of pharmaceutical research.
Next, drawing on recent history, they propose dividing drug companies into drug discovery/development firms and drug marketing/distribution firms, just as electric utility firms were separated into generation and distribution companies in the 1990s.
Following the utility model, Finkelstein and Temin propose establishing an independent, public, non-profit Drug Development Corporation (DDC), which would act as an intermediary between the two new industry segments — just as the electric grid acts as an intermediary between energy generators and distributors.
The DDC also would serve as a mechanism for prioritizing drugs for development, noted Finkelstein.
“It is a two-level program in which scientists and other experts would recommend to decision-makers which kinds of drugs to fund the most. This would insulate development decisions from the political winds,” he said.
Finkelstein and Temin’s plan would also insulate drug development from the blockbuster mentality, which drives companies to invest in discovering a billion-dollar drug to offset their costs.
An example of the blockbuster mentality is developing a new drug for hypertension, one that varies only slightly from those already on the market, but that can bring in huge profits if aggressively marketed.
For Finkelstein, a physician, and Temin, an economist, societal needs for medicines are swiftly extending beyond national boundaries: Diseases affecting the developing world–afflicting people too poor to make drug development attractive for businesses–will soon affect health inside the United States.
“Global travel and climate change both require that U.S. drug development and innovation policy rethink the way drugs are developed, and for whom. Air travel, migrations, a global workforce–all these mean unusual diseases could become usual here,” Temin noted.
Climate change also may affect drugs their proposed DDC would select for funding.
“Especially in the southern states, tropical diseases are likely to increase with global warming, and people will need treatments for them. In our plan, the DDC would encourage research in advance of the market – and, we hope, in advance of disaster,” he said.
Public release date: 17-Mar-2008
New study: Pycnogenol improves memory in elderly
New research accepted for publication in the Journal of Psychopharmacology, demonstrates Pycnogenol, (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, improves the memory of senior citizens.
The study results revealed Pycnogenol improved both numerical working memory as well as spatial working memory using a computerized testing system. The research was presented last week at the Oxygen Club of California 2008 World Congress on Oxidants and Antioxidants in Biology in Santa Barbara, CA.
“These results support research from a range of disciplines that suggest that antioxidants may have an effect in preserving or enhancing specific mental functions,” said Dr. Con Stough, lead researcher of the study. “Cognitive research in this area specifically indicates that the putative benefits associated with antioxidant supplementation are associated with memory.”
The double-blind, placebo controlled, matched pairs study, which was held at the Centre for Neuropsychology at Swinburne University, Melbourne Australia, examined the effects of Pycnogenol on a range of cognitive and biochemical measures in 101 senior individuals aged 60-85 years old. The study also examined the ‘oxidative stress’ hypothesis of ageing and neurological degeneration as it relates to normal changes in cognition in elderly individuals. Participant screening for the study included medical history and cognitive assessment. Participants consumed a daily dose of 150mg of Pycnogenol for a three-month treatment period and were assessed at baseline then at one, two and three months of the treatment. The control and Pycnogenol groups were matched by age, sex, BMI, micronutrient intake and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory and psycho-motor performance.
Blood samples were taken from subjects and after 3 months treatment a marker known as F2-isoprostanes significantly decreased with Pycnogenol, but not in the placebo group. F2-isoprostanes develop by oxidation of unsaturated fatty acids, which are present in particularly high quantities in nerve cell membranes. The coincidence of Pycnogenol significantly improving memory after three months and the oxidation of nerve membranes being significantly inhibited suggests that the antioxidant activity of Pycnogenol plays a major role for the clinical effects.
According to Dr. Stough, “The antioxidant Pycnogenol had beneficial cognitive and biochemical effects for elderly individuals. Participants in the Pycnogenol groups showed improvement relative to the controls with the effects becoming evident from the second to third months of the Pycnogenol treatment.”
Research on Pycnogenol’s cognitive function benefits are currently being investigated further. Several recent research studies on Pycnogenol studied the extract’s effects on Attention Deficit Disorders including ADD and ADHD. Findings published in the Journal of European Child & Adolescent Psychiatry showed Pycnogenol reduced ADHD symptoms such as hyperactivity and improved attention, concentration and motor-visual coordination in children with ADHD.
Public release date: 18-Mar-2008
Pneumococcal disease rates down significantly post-vaccine
Since the approval of a vaccine against pneumococcal bacteria for young children in 2000, rates of invasive pneumococcal disease (IPD) are down significantly in all age groups, while rates of IPD caused by non-vaccine strains are modestly on the rise. Researchers from the Centers for Disease Control and Prevention (CDC) report their results today (March 18) at the 2008 International Conference on Emerging Infectious Diseases in Atlanta, Georgia.
“This vaccine is continuing to provide a very substantial public health impact 6 years after its introduction. We estimate that between 2001 and 2006, 170,000 cases and 9,800 deaths were prevented as a result of this vaccine,” says Matthew Moore of the CDC, a lead researcher on the study.
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.
The CDC has been tracking the incidence of IPD, the most severe form of the disease – defined as meningitis or a bloodstream infection, which can include some cases of pneumonia – since the introduction of the vaccine. Moore and his colleagues compared rates of IPD in 2006 with reported rates for 1998-1999, just before PCV7 was introduced.
The researchers found a significant decline in IPD rates for all age groups (-78%, under 5 years; -38%, 5-17 years; -39%, 18-49 years; -14%, 50-64 years; -32%, 65-79 years; and -42%, 80 years and older) with even greater declines in IPD caused by those strains included in the PCV7 vaccine. The incidence of IPD caused by strains not included in the vaccine rose by 40%. One of the non-vaccine strains, 19A showed an increase of 264%, but Moore cautions that because these strains were relatively uncommon before the introduction of the vaccine, the increase in actual numbers is still small.
“PCV continues to provide impressive public health benefits after introduction. Disease caused by non-PCV7 serotypes, especially 19A, is emerging and accounts for nearly all IPD. Newer conjugate vaccines targeting more serotypes are needed to further reduce IPD,” says Moore.
The introduction of PCV7 may have also helped solve an enduring mystery associated with IPD. The incidence of the disease is seasonal with rates running 5 times higher in the winter, but there is also a sharp but unexplained spike that occurs annually in older adults during the weeks around January 1.
Nicholas Walter of the CDC and his colleagues analyzed 11 years worth of IPD surveillance data and noticed that after the introduction of PCV7 the spikes were much less severe. Since PCV7 is used in children, they had to figure that into the equation somehow. Based on the data, Walter and his colleagues now believe the annual spike may be the result of older adults being exposed to colonized children when families get together for the winter holidays.
“Timing of the spikes and the predominance of older adults suggest the spikes may be related to older adults’ increased exposure to young children around the winter holidays,” says Walter, who also presented his data at the meeting. The observation that spikes diminished after introduction of PCV7 gives further indication that vaccination of children limits disease not only in children, but also in adults. Many of these infections may be preventable with pneumococcal polysaccharide vaccine, which targets 23 different serotypes and is recommended for all adults 65 years of age and older.
Ralph’s Note – There is a danger of eliminating a bacteria, or virus. To only have a more deadly version arise. Think of it as seats at a busy movie theater. You put your feet up on the chair in front of you, to intimidate the individual with the sloppy hair to move. Only to have an eight foot giant to take the seat afterwards. Those seats will always be full, as there will always be bacteria. Just be as certain as possible, not to exchange one danger, for a nightmare.
Public release date: 18-Mar-2008
What effect does melatonin have in colitis?
In rats with experimental colitis, the marked increase in bacterial translocation in postcolitis rats has been reversed by melatonin administration. This is due to melatonin’s anti-inflammatory and anti-apoptotic effects.
Using an elegant study design, including experimental colitis model, this research was performed by doctors from the Departments of General Surgery, Microbiology, Pathology and Biochemistry of the Faculty of Medicine at the University of Erciyes, Kayseri, Turkey.
This study, performed by a team led by Dr. Alper Akcan, is described in a research article in the February 14 2008 issue of the World Journal of Gastroenterology.
According to the authors, the purpose of this study was to determine whether exogenously administered melatonin had any influence on the impairment of bacterial translocation and apoptosis in experimental colitis. To their knowledge, their study is the first one showing the relation between colitis, melatonin, and bacterial translocation.
The exact pathogenesis in inflammatory bowel disease (IBD) is poorly understood, but evidence exists that IBD involves interactions between immune system, genetic susceptibility and the environment. In IBDs, the intestinal mucosal barrier is disrupted by inflammation and ulceration. In these circumstances, translocation of enteric bacteria and their products through the bowel wall to extra-intestinal sterile sites may result. Bacterial translocation may cause secondary infection of intra-abdominal inflammatory processes, such as intra-abdominal abscesses, or peritonitis. Recent studies have, however, shown the important role of anti-inflammatory and antioxidant agents, including melatonin, in IBDs.
Melatonin is an agent that promotes sleep and is produced at night by the pineal gland. While produced primarily in the pineal gland, melatonin can also be found in cells of the bone marrow and the gastrointestinal tract and plays a fundamental role in the neuroimmuno-endocrine system. In most of the published studies an antioxidative effect, improved microcirculation and a stimulation of intestinal epithelium may also apply in the preventive or therapeutic effect of melatonin on the symptoms of colitis induced in rats has been documented.
Further research should explain the similar effects of melatonin in humans.
Public release date: 18-Mar-2008
Do bacterial combinations result in enhanced cytokine production? No!
Probiotic bacteria, defined as living microorganisms that have beneficial effects on human health, have been used for the prevention and treatment of a diverse range of disorders. However, the ways in which probiotic bacteria elicit their health effects are not fully understood. One of the action mechanisms could be the ability to induce cytokines that further regulate innate and adaptive immune responses. At present there is only a limited amount of comparative data available on the ability of different probiotic strains to induce cytokine responses within the same experimental system. In addition, the effect of probiotic bacterial combinations on cytokine production in vitro is not well documented although bacterial combinations have been used in many clinical trials.
A recent study revealed that probiotic bacteria seem to direct immune responses to either a Th1 type or in anti-inflammatory way in a bacterial genera-specific manner in human leukocyte cell culture. Not all bacterial combinations resulted in enhanced cytokine production suggesting that different bacteria — whether gram-positive or gram-negative — compete with each other during host cell interactions. Results of this study can be exploited for designing new probiotic products that have specific health effects.
This study, performed by the groups of Dr Korpela and Professor Julkunen and to be published in February 28, 2008 in issue 8 of the World Journal of Gastroenterology. The work was carried out in collaboration with National Public Health Institute (Finland), Valio Research Centre (Finland) and University of Helsinki (Finland).
This is one of the few studies that have compared the cytokine patterns of probiotic bacteria and their combinations within the same experimental setting. It was found that probiotic bacteria induce differential cytokine responses dependent on the bacterial genera. In addition it was found that novel probiotic S. thermophilus and Leuconostoc strains are more potent inducers of Th1 type cytokines IL-12 and IFN-ƒ× than the probiotic Lactobacillus strains presently in use in probiotic products. The use of bacterial combinations did not result in enhanced cytokine production.
More detailed information on the cytokine patterns elicited by probiotic bacteria may help in designing probiotics for specific preventative or therapeutic purposes.
Public release date: 18-Mar-2008
Grape skin compound fights the complications of diabetes
Resveratrol in grape skins could stop diabetic complications such as heart disease, retinopathy and nephropathy, research finds
Research carried out by scientists at the Peninsula Medical School in the South West of England has found that resveratrol, a compound present naturally in grape skin, can protect against the cellular damage to blood vessels caused by high production of glucose in diabetes, according to a paper published in the science journal “Diabetes, Obesity and Metabolism” this week.
The elevated levels of glucose that circulate in the blood of patients with diabetes causes micro- and macrovascular complications by damaging mitochondria, the tiny power plants within cells responsible for generating energy. When they are damaged they can leak electrons and make highly damaging ‘free radicals’.
Complications that can result when this happen include nephropathy (kidney disease), heart disease and retinopathy (which if left untreated can lead to blindness).
Resveratrol stops the damage by helping cells make protective enzymes to prevent the leakage of electrons and the production of toxic ‘free radicals’.
As well as being naturally present in grape skins, resveratrol is also present in seeds, peanuts and red wine.
Dr. Matt Whiteman, Principal Investigator and Senior Lecturer at the Institute of Biomedical and Clinical Science, Peninsula Medical School, commented: “Resveratrol’s antioxidant effects in the test tube are well documented but our research shows the link between high levels of glucose, its damaging effect on cell structure, and the ability of resveratrol of protect against and mend that damage.”
He added: “Resveratrol or related compounds could be used to block the damaging effect of glucose which in turn might fight the often life threatening complications that accompany diabetes. It could well be the basis of effective diet-based therapies for the prevention of vascular damage caused by hyperglycaemia in the future.”
Public release date: 18-Mar-2008
Scientists successfully awaken sleeping stem cells
Boston, MA—Scientists at Schepens Eye Research Institute have discovered what chemical in the eye triggers the dormant capacity of certain non-neuronal cells to transform into progenitor cells, a stem-like cell that can generate new retinal cells. The discovery, published in the March issue of Investigative Ophthalmology and Visual Science (IOVS), offers new hope to victims of diseases that harm the retina, such as macular degeneration and retinitis pigmentosa.
“This study is very significant. It means it might be possible to turn on the eye’s own resources to regenerate damaged retinas, without the need for transplanting outside retinal tissue or stem cells,” says Dr. Dong Feng Chen, associate scientist at Schepens Eye Research Institute and Harvard Medical School, and the principal investigator of the study. “If our next steps work in animal disease models, we believe that clinical testing could happen fairly quickly.”
Scientists have long been aware of Müller cells (which exist in great abundance in the eye) and have generally assumed that they were responsible for keeping retinal tissue protected and clear of debris. In recent years, however, researchers have reported that these cells sometimes exhibit progenitor cell behavior and re-enter the cell cycle (dividing and differentiating into other type of cells). Progenitor cells are similar to stem cells but are more mature and are more limited in the number of cells types they can become.
But until this study, scientists have not understood what triggers the transformation. In their study, Chen and her team observed that when the naturally occurring chemicals known as glutamate and aminoadipate (which is a derivative of glutamate) were injected into the eye, the Müller cells began to divide and proliferate. Not certain if these chemicals directly signaled the transformation, they tested them in the laboratory and in mice.
They added each chemical separately to cultures of pure Müller cells and injected each into the space below the retina in healthy mice. In both cases, the cells became progenitor cells and then changed into retinal cells. And with aminoadipate, the newly minted retinal cells migrated to where they might be needed in the retina and turned into desirable cell types. Specifically, they showed that by injecting the chemical below the retina, the cells give rise to new photoreceptors – the type of cells that are lost in retinitis pigmentosa or macular degeneration, as a result, leading to blindness.
The team’s next step will be to test this process in animals that have been bred to have diseases that mimic macular degeneration and retinitis pigmentosa. The goal would be to learn if damaged retinas regenerate and vision improves. The team will likely use just aminoadipate because it only binds with Müller cells without the side effects of glutamate, which can actually harm retina cells in large doses.
“We believe that a drug created from the chemical aminoadipate or a similar compound has great potential for healing damaged retinas,” says Chen.
Public release date: 18-Mar-2008
Only two per cent of paediatric drug trials reported using independent safety monitoring
Only two per cent of paediatric drug trials reported using independent safety monitoring committees that can help lead to the early detection of adverse drug reactions, according to a major review published in the journal Acta Paediatrica.
Child health researchers from The University of Nottingham carried out a detailed analysis of 739 international drug trials published between 1996 and 2002, to see what safety measures were in place to monitor levels of adverse drug reactions.
While 74 per cent of the drug trials described how safety monitoring was performed during the study, only two per cent — 13 studies out of 739 — had independent safety monitoring committees.
Lead author Dr Helen Sammons, an Associate Professor of Child Health in the University’s Academic Division of Child Health, based at Derbyshire Children’s Hospital, said: “We were very surprised by the low level of trials that had independent safety monitoring committees and are urging pharmaceutical companies to include these in all future trials involving children.
“It is essential that drugs are developed for use in children and clinical trials need to continue. They are vital because they increase the chance of picking up adverse reactions before drugs are introduced into general clinical practice.”
Dr Sammons and her colleagues found that:
Seven out of ten trials reported adverse events and a fifth of the trials reported a serious adverse event, ie. an untoward medical occurrence, not necessarily related to a drug.
Adverse drug reactions were reported in just under 37 per cent of trials, with 11 per cent of trials reporting moderate or severe adverse drug reactions.
Six clinical trials — which all had safety monitoring committees — were terminated early because of significant drug toxicity.
Deaths were reported in 11 per cent of the trials, but the majority were thought to be unrelated to the drug use.
Death rates were highest in trials involving newborn babies, with 56 per cent of the 99 trials included reporting a death.
Other major specialities in which deaths were reported included infectious diseases, neurology, respiratory and kidney problems.
Only papers published in English on the Medline database during the seven-year study period were included and the authors excluded studies that covered HIV and cancer because of high deaths rates from the actual diseases.
Just over half of the studies compared a drug with a placebo — dummy — and a further 35 per cent involved a new medicine. A smaller percentage, 26 per cent, involved a direct comparison between two established drugs. Some of the trials included adults as well as children.
Studies reporting severe drug toxicity problems came from a wide range of countries, including Argentina, Belgium, Canada, Chile, China, France, India, Israel, Italy, Japan, Netherlands, South Africa, Sweden, Taiwan, Thailand, Turkey, UK and the USA.
Adverse drug reactions included bleeding, high blood pressure, seizures, psychosis, suicide, acute renal failure and death.
The researchers stress that clinical drug trials in children are essential for the development of medicines and to provide evidence of the best treatments for specific conditions. But they feel that greater safety measures and awareness of the risk is essential.
“We need to test drugs on children as the only other options are to use unlicensed drugs or prescribe drugs that have been licensed for adults off-label — outside the terms of their licence,” said Dr Sammons.
“But we feel that the small number of studies that reported having safety monitoring committees was unacceptable. It is invaluable to have an independent monitor who can swiftly question any adverse drug reactions or differences in illness and death rates between groups taking part in the clinical trials.
“Parents also need to be made aware of the risks of adverse drug reactions when a child takes any medicine so that they can make informed decisions that balance those risks against the possible benefits the drug may provide their child.
“In a drug trial this should include information on the mechanisms that will be used during the clinical trial to safeguard the children taking part.”
Dr Sammons points out that the number of paediatric drug trials is likely to rise in the European Union, following new legislation that provides pharmaceutical companies with a valuable financial incentive – a six-month extension to their exclusive manufacturing licence for a drug if children are included in the clinical trials. Similar legislation has been in place in the USA for over five years and has led to an increase in drug trials that include children.
She added: “There is general agreement by paediatric health professionals, regulatory authorities and the pharmaceutical industry, as well as politicians and parents, that drug trials are essential in order to improve drug therapies.
“We are calling for all paediatric drug trials to include independent safety monitoring committees to ensure that this vital work is carried out in a way that minimises risks, and maximises benefits, for the children taking part.”