Health Research Report
144th Issue 14 DEC 2012
Compiled By Ralph Turchiano
www.facebook.com/engineeringevil
Editors top five:
Too few
In this Issue:
1. Extended sleep reduces pain sensitivity
2. Lithium restores cognitive function in Down syndrome mice
3. Food allergies ? Pesticides in tap water might be to blame
4. New evidence on how compound found in red wine can help prevent cancer
5. Fish Oil Helps Heal Bed Sores of the Critically Ill
6. In vitro study finds digested formula, but not breast milk, is toxic to cells
7. Caffeinated coffee linked to lower risk of some oral cancers
8. Pharmacy researcher finds most popular weight-loss drug strongly alters other drug therapies
9. Vegetable compound could become ingredient to treating leukemia
10. Changes in the gut bacteria protect against stroke
Extended sleep reduces pain sensitivity
Increasing sleep time improves daytime alertness and reduces pain sensitivity
DARIEN, IL – A new study suggests that extending nightly sleep in mildly sleepy, healthy adults increases daytime alertness and reduces pain sensitivity.
“Our results suggest the importance of adequate sleep in various chronic pain conditions or in preparation for elective surgical procedures,” said Timothy Roehrs, PhD, the study’s principal investigator and lead author. “We were surprised by the magnitude of the reduction in pain sensitivity, when compared to the reduction produced by taking codeine.”
The study, appearing in the December issue of the journal SLEEP, involved 18 healthy, pain-free, sleepy volunteers. They were randomly assigned to four nights of either maintaining their habitual sleep time or extending their sleep time by spending 10 hours in bed per night. Objective daytime sleepiness was measured using the multiple sleep latency test (MSLT), and pain sensitivity was assessed using a radiant heat stimulus.
Results show that the extended sleep group slept 1.8 hours more per night than the habitual sleep group. This nightly increase in sleep time during the four experimental nights was correlated with increased daytime alertness, which was associated with less pain sensitivity.
In the extended sleep group, the length of time before participants removed their finger from a radiant heat source increased by 25 percent, reflecting a reduction in pain sensitivity. The authors report that the magnitude of this increase in finger withdrawal latency is greater than the effect found in a previous study of 60 mg of codeine.
According to the authors, this is the first study to show that extended sleep in mildly, chronically sleep deprived volunteers reduces their pain sensitivity. The results, combined with data from previous research, suggest that increased pain sensitivity in sleepy individuals is the result of their
Lithium restores cognitive function in Down syndrome mice
Down syndrome is a neurodevelopmental disorder that is the leading cause of genetically defined intellectual disability. In the brain, Down syndrome results in alterations in the connections between neurons and a reduction in the development of new neurons (neurogenesis) that usually occurs during learning. In this issue of the Journal of Clinical Investigation, researchers led by Laura Gasparini at the Istituto Italiano di Tecnologia in Genova, Italy report that lithium, a drug commonly used for the treatment of mood disorders in humans, restores neurogenesis in the hippocampus, a part of the brain strongly associated with learning and memory. Lithium also significantly improved the performance of Down syndrome mice in tasks measuring contextual learning, spatial memory, and object discrimination. These results suggest that lithium-based therapies may help Down syndrome patients.
Food allergies? Pesticides in tap water might be to blame
New study finds chemicals used for water purification can lead to food allergies
ARLINGTON HEIGHTS, Ill. (December 3, 2012) – Food allergies are on the rise, affecting 15 million Americans. And according to a new study published in the December issue of Annals of Allergy, Asthma and Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI), pesticides and tap water could be partially to blame.
The study reported that high levels of dichlorophenols, a chemical used in pesticides and to chlorinate water, when found in the human body, are associated with food allergies.
“Our research shows that high levels of dichlorophenol-containing pesticides can possibly weaken food tolerance in some people, causing food allergy,” said allergist Elina Jerschow, M.D., M.Sc., ACAAI fellow and lead study author. “This chemical is commonly found in pesticides used by farmers and consumer insect and weed control products, as well as tap water.”
Among 10,348 participants in a US National Health and Nutrition Examination Survey 2005-2006, 2,548 had dichlorophenols measured in their urine and 2,211 were included into the study. Food allergy was found in 411 of these participants, while 1,016 had an environmental allergy.
“Previous studies have shown that both food allergies and environmental pollution are increasing in the United States,” said Dr. Jerschow. “The results of our study suggest these two trends might be linked, and that increased use of pesticides and other chemicals is associated with a higher prevalence of food allergies.”
While opting for bottled water instead of tap water might seem to be a way to reduce the risk for developing an allergy, according to the study such a change may not be successful.
“Other dichlorophenol sources, such as pesticide-treated fruits and vegetables, may play a greater role in causing food allergy,” said Dr. Jerschow.
According to the Centers for Disease Control and Prevention, an increase in food allergy of 18 percent was seen between 1997 and 2007. The most common food allergens are milk, eggs, peanuts, wheat, tree nuts, soy, fish, and shellfish.
Food allergy symptoms can range from a mild rash to a life-threatening reaction known as anaphylaxis. The ACAAI advises everyone with a known food allergy to always carry two doses of allergist prescribed epinephrine. A delay in using epinephrine is common in severe food allergic reaction deaths.
New evidence on how compound found in red wine can help prevent cancer
International conference at the University of Leicester will show how resveratrol can prevent cancer, heart disease and diabetes
University of Leicester scientists will present groundbreaking new evidence about how a chemical found in red wine can help prevent cancer on Wednesday, December 5.
Experts from around the world are set to attend Resveratrol 2012, a major conference at the University which will assess the latest advances in the study of resveratrol – a compound found in the skins of red grapes.
The conference will feature new findings based on the last two years of research, which show how the chemical can help prevent cancer, heart disease and diabetes.
The event follows the first international conference on resveratrol, held in 2010 in Denmark, and evidence from more than ten clinical trials held since will be presented and discussed.
Although the potential health benefits of resveratrol have been known for some time, it has not yet been proven that resveratrol can be effective in humans and the best dose to give remains unknown – meaning that its widespread use cannot safely be recommended at the moment.
Researchers at the University of Leicester have been researching the levels of resveratrol which can be beneficial in preventing cancer.
Using laboratory models, they have found that a daily amount of resveratrol equivalent to two glasses of wine can halve the rate of bowel tumors.
Professor Karen Brown, a member of the University’s Cancer Biomarkers and Prevention Group and one of the organisers of Resveratrol 2012, said: “This is the second conference that brings together all the world experts in resveratrol. We have got a fantastic line up covering cancer, heart disease, diabetes, neurological diseases and life extension.
“At the University of Leicester, we want to see how resveratrol might work to prevent cancer in humans. Having shown in our lab experiments that it can reduce tumour development we are now concentrating on identifying the mechanisms of how resveratrol works in human cells.”
The Leicester researchers now hope to take their findings from the lab to the next stage by carrying out clinical trials to find the optimum level of resveratrol in humans.
Professor Brown added: “A lot of people take resveratrol as a supplement, but at the moment we don’t know how it works or on whom it can work until we have more information – we don’t even know the best dose you should take. It has been shown that high doses of resveratrol may potentially interfere with other medication. With all the exciting new studies that are being done – especially the clinical trials – I hope we’ll have a clearer picture in the next few years.”
The conference will include more than 65 lectures, presentations and posters by different researchers from all over the world.
As well as offering opportunities for knowledge sharing and networking, the conference will produce a selection of reports with the latest update on global resveratrol research, as well as the next set of recommendations for the coming year’s scientific research and the use of resveratrol.
Fish Oil Helps Heal Bed Sores of the Critically Ill
Tuesday, December 4, 2012
Tel Aviv University research finds a 20-25 percent reduction in pressure ulcers with a fish oil enriched diet
Chock-full of Omega-3 fatty acids and antioxidants, fish oil can help lower blood pressure, reduce inflammation in the skin and joints, and promote healthy fetal development. Now a Tel Aviv University researcher has found that it has a positive effect on bedsores, too.
A common problem in critically ill patients, bedsores result from constant pressure on the skin and underlying tissue due to prolonged sitting or lying down. Painful and prone to infection, the pressure ulcers need to be healed, says Prof. Pierre Singer of the Sackler Faculty of Medicine. With Ph.D. candidate Miriam Theilla at the Rabin Medical Center, he designed a randomized experiment to determine the impact of dietary fish oil supplements on the bedsores of critically ill patients.
After a three week period of adding eight grams of fish oil to their patients’ daily diet, the researchers found not only a significant lessening of pain and discomfort from bedsores — a 20 to 25 percent improvement, according to the Pressure Ulcer Scale for Healing — but also a more efficient immune system and a reduction to inflammation throughout the body. The results were reported in the British Journal of Nutrition and the American Journal of Critical Care.
Boosting the immune system
Inspired by the results of a previous study showing that dietary fish oil supplements for critically ill patients raised oxygen levels in body tissues, Prof. Singer and his fellow researchers sought to determine whether the supplement could also help heal bedsores, which are also formed by a lack of oxygen, reduced blood flow, and skin wetness.
To test this theory, the researchers developed a randomized study with 40 critically ill patients. Half the patients were given standard hospital diets, and the rest had a daily addition of eight grams of fish oil added in their food. After a three-week period, the patients in the fish oil group had an average of 20 to 25 percent improvement in the healing of their bedsores compared to the control group.
Beyond the size of the bedsores, the researchers also measured different immune parameters and found that the patients in the fish oil group had experienced a boost in their immune system and a reduction in swelling. “We saw a modification in the expression of a group of molecules associated with directing leukocytes, or white blood cells, in the direction of the wound, which could explain the improved healing,” explains Prof. Singer. In addition, researchers noted a significant decrease in the amount of C-reactive protein in the blood, which is associated with inflammation and linked to viral and bacterial infections, rheumatic diseases, tissue injury, and necrosis.
Natural pain management?
Next, Prof. Singer and his fellow researchers plan to explore the use of fish oil as a method of natural pain management. By measuring the intensity of pain experience in post-surgical patients who have undergone either knee or hip replacements and comparing it to the amount of fish oil the patient has received, they hope to determine whether the nutrient-rich oil can also reduce their patients’ suffering.
In vitro study finds digested formula, but not breast milk, is toxic to cells
Findings may help explain development of fatal condition in premature infants
Free fatty acids created during the digestion of infant formula cause cellular death that may contribute to necrotizing enterocolitis, a severe intestinal condition that is often fatal and occurs most commonly in premature infants, according to a study by University of California, San Diego bioengineers. Their report, which was based on in vitro tests comparing the digestion of fresh human breast milk and nine different infant formulas, was published online in the journal Pediatric Research.
Scientists have long known that premature infants fed formula are more likely to develop necrotizing enterocolitis than those fed breast milk. The condition is the leading cause of death from gastrointestinal diseases in premature infants, but the underlying mechanism has not been understood. Alexander Penn, a research scientist working in the Microcirculation Laboratory of bioengineering Professor Geert Schmid-Schönbein from the UC San Diego Jacobs School of Engineering, believes they have come closer to an answer.
Penn and others had previously determined that the partially digested food in a mature, adult intestine is capable of killing cells, due to the presence of free fatty acids which have a “detergent” capacity that damages cell membranes. The intestines of healthy adults and older children have a mature mucosal barrier that may prevent damage due to free fatty acids. However, the intestine is leakier at birth, particularly for preterm infants, which could be why they are more susceptible to necrotizing enterocolitis.
Therefore, the researchers wanted to know what happens to breast milk as compared to infant formula when they are exposed to digestive enzymes. They “digested,” in vitro, infant formulas marketed for full term and preterm infants as well as fresh human breast milk using pancreatic enzymes or fluid from an intestine. They then tested the formula and milk for levels of free fatty acids. They also tested whether these fatty acids killed off three types of cells involved in necrotizing enterocolitis: epithelial cells that line the intestine, endothelial cells that line blood vessels, and neutrophils, a type of white blood cell that is a kind of “first responder” to inflammation caused by trauma in the body.
Overwhelmingly, the digestion of formula led to cellular death, or cytotoxicity – in less than 5 minutes in some cases – while breast milk did not. For example, digestion of formula caused death in 47 percent to 99 percent of neutrophils while only 6 percent of them died as a result of milk digestion. The study found that breast milk appears to have a built-in mechanism to prevent cytotoxicity. The research team believes most food, like formula, releases high levels of free fatty acids during digestion, but that breast milk is digested in a slower, more controlled, process.
Currently, many neonatal intensive care units are moving towards formula-free environments, but breastfeeding a premature infant can be challenging or physically impossible and supplies of donor breast milk are limited. To meet the demand if insufficient breast milk is available, less cytotoxic milk replacements will need to be designed in the future that pose less risk for cell damage and for necrotizing enterocolitis, the researchers concluded.
This may be of benefit not only to premature infants, but also to full-term infants at higher risk for disorders that are associated with gastrointestinal problems and more leaky intestines, such as autism spectrum disorder. Dr. Sharon Taylor, a professor of pediatric medicine at UC San Diego School of Medicine and a pediatric gastroenterologist at Rady Children’s Hospital, San Diego, said the study offers more support to an already ongoing push by hospitals, including neonatal intensive care units, to encourage breastfeeding even in more challenging circumstances in the NICU. For patients who are too premature or frail to nurse, Dr. Taylor said hospital staff should provide consultation and resources to help mothers pump breast milk that can be fed to the baby through a tube.
The research was carried out in collaboration with Dr. Taylor, Karen Dobkins of the Department of Psychology, and Angelina Altshuler and James Small of the Department of Bioengineering at UC San Diego and was funded by the National Institutes of Health (NS071580 and GM85072). The researchers conclude that breast milk has a significant ability to reduce cytotoxicity that formula does not have. One next step is to determine whether these results are replicated in animal studies and whether intervention can prevent free fatty acids from causing intestinal damage or death from necrotizing enterocolitis.
Caffeinated coffee linked to lower risk of some oral cancers
Studies link consumption of more than 4 cups per day to significantly lower risk of death from some cancers
ATLANTA – December 10, 2012—A new American Cancer Society study finds a strong inverse association between caffeinated coffee intake and oral/pharyngeal cancer mortality. The authors say people who drank more than four cups of caffeinated coffee per day were at about half the risk of death of these often fatal cancers compared to those who only occasionally or who never drank coffee. The study is published online in the American Journal of Epidemiology. The authors say more research is needed to elucidate the biologic mechanisms that could be at work.
Previous epidemiologic studies have suggested that coffee intake is associated with reduced risk of oral/pharyngeal cancer. To explore the finding further, researchers examined associations of caffeinated coffee, decaffeinated coffee, and tea intake with fatal oral/pharyngeal cancer in the Cancer Prevention Study II, a prospective U.S. cohort study begun in 1982 by the American Cancer Society.
Among 968,432 men and women who were cancer-free at enrollment, 868 deaths due to oral/pharyngeal cancer occurred during 26 years of follow-up. The researchers found consuming more than four cups of caffeinated coffee per day was associated with a 49 percent lower risk of oral/pharyngeal cancer death relative to no/occasional coffee intake (RR 0.51, 95% confidence interval [CI] 0.40-0.64). A dose-related decline in relative risk was observed with each single cup per day consumed. The association was independent of sex, smoking status, or alcohol use. There was a suggestion of a similar link among those who drank more than two cups per day of decaffeinated coffee, although that finding was only marginally significant. No association was found for tea drinking.
The findings are novel in that they are based specifically upon fatal cases of oral/pharyngeal cancer occurring over a 26-year period in a population of prospectively-followed individuals who were cancer-free at enrollment in Cancer Prevention Study II.
“Coffee is one of the most widely consumed beverages in the world, and contains a variety of antioxidants, polyphenols, and other biologically active compounds that may help to protect against development or progression of cancers,” said lead author Janet Hildebrand, MPH. “Although it is less common in the United States, oral/pharyngeal cancer is among the ten most common cancers in the world. Our finding strengthens the evidence of a possible protective effect of caffeinated coffee in the etiology and/or progression of cancers of the mouth and pharynx. It may be of considerable interest to investigate whether coffee consumption can lead to a better prognosis after oral/pharyngeal cancer diagnosis.”
Pharmacy researcher finds most popular weight-loss drug strongly alters other drug therapies
KINGSTON, R.I.— December 10, 2012 – A University of Rhode Island researcher has discovered that the weight-loss drug orlistat, known by the brand names Xenical and Alli, inhibits a key enzyme that may lead to “severe toxicity of internal organs such as the liver and kidney.” The inhibition is irreversible and can be caused by a low level of the drug.
Professor Bingfang Yan’s study funded by the National Institutes of Health, also found that the drug alters efficacy of medicines, and particularly limits the effectiveness of some anti-cancer drugs.
Part of the research results will be published in the journal, Biochemical Pharmacology, which has the article posted on its website today. Yan also alerted the U.S. Food and Drug Administration to his findings.
Orlistat, which was originally approved by the FDA in 1999 as the prescription drug Exenical, was approved in 2007 as the over-the-counter medication Alli. It has been the most commonly used medicine to treat obesity for more than a decade, Yan said.
“Since it has been available over–the-counter, there has been a drastic increase of toxicity among patients using the drug,” Yan said. “It has been linked to severe liver failure, acute pancreatic failure and acute renal (kidney) failure.”
Yan said orlistat works in the intestinal tract by preventing fat from being absorbed by the body. It is generally accepted that orlistat remains in the intestine and that the body does not absorb it.
“But orlistat is reportedly absorbed, and certainly internal organs such as the liver and kidney are exposed to this drug upon absorption,” he said.
The study showed that the drug is a potent inhibitor of carboxylesterase-2, which is a major detoxification enzyme in the liver, kidney and gastrointestinal track. “When the activity of this enzyme drop in those organs, toxicity increases or the efficacy of some drugs are altered,” Yan said.
The enzyme is known to metabolize a wide range of medicines including aspirin and the cancer drugs irinotecan and pentyl carbamate of p-aminobenzyl carbamate of doxazolidine.
“This study shows that orlistat profoundly alters the therapeutic potential of the anti-cancer drugs,” Yan said. “In the case of the anti-cancer drugs, it weakens their effectiveness.”
Prior or co-presence of orlistat with one of the anti-cancer drugs resulted in cancer cells being far more prolific.
“Alli-based interactions can be key factors in the efficacy of medicines,” Yan said.
Yan was also interested in Alli’s effects on aspirin and its use as a blood thinner. “Aspirin is used to treat blood clots. Yan predicated: “Orlistat would increase the therapeutic potential of aspirin, which may increase the tendency of bleeding.”
This isn’t the first time that Yan has found critical drug interactions in his studies.
In 2006, he discovered that the anti-viral drug Tamiflu would be rendered ineffective in patients also taking the anti-clotting drug Plavix. His published findings have resulted in new dosing regimens for patients who need both drugs.
Yan is one of the authors of the 6-volume Encyclopedia of Drug Metabolism and Interactions. This state-of-the-art integrated reference represents a global effort and presents more than 120 chapters by prominent authors from 11 different countries: the United States, Canada, United Kingdom, Germany, Australia, Singapore, India, Japan, France, Denmark, and Switzerland.
Vegetable compound could become ingredient to treating leukemia
HOUSTON – (Dec. 12, 2012) – It looks like your mother was on to something when she said, “Eat your vegetables!”
A concentrated form of a compound called sulforaphane found in broccoli and other cruciferous vegetables has been shown to reduce the number of acute lymphoblastic leukemia cells in the lab setting, said researchers at Baylor College of Medicine. The findings appear in the current edition of PLOS ONE.
“Acute lymphoblastic leukemia is a type of cancer of the white blood cells common in children,” said Dr. Daniel Lacorazza, assistant professor of pathology & immunology. “There is about an 80 percent cure rate, but some children don’t respond to treatment. For those cases, we are in need of alternative treatments.”
Lacorazza and his colleagues focused on purified sulforaphane, a natural compound found in broccoli believed to have both preventive and therapeutic properties in solid tumors. Studies have shown that people who eat a diet rich in cruciferous vegetables have a lower risk of some cancers.
“There have not been definitive studies showing how this compound interacts with blood cancers,” Lacorazza said.
To study how this compound would act on acute lymphoblastic leukemia, researchers, led by Dr. Koramit Suppipat, lead author of the study who performed this work while a clinical fellow in the Texas Children’s Cancer and Hematology Centers, incubated human-derived leukemic cell lines and primary lymphoblasts from pediatric patients with the compound. The cancer cells died while the healthy cells obtained from healthy donors were unaffected. Studies tested in pre-clinical mouse models showed similar results.
Lacorazza said the compound works by entering the cells and reacting with certain proteins. More studies will be needed, but researchers believe this compound could one day be used as a treatment option in combination with current therapies. They also are working to determine which proteins are affected by sulforaphane and how. This could identify a new treatment target that might be affected by other types of cancer cells as well.
“Sulforaphane is a natural product. However, what we used in this study is a concentrated purified form,” said Lacorazza. “So while eating cruciferous vegetables is good for you, it will not have the same effect as what we saw in the lab.”
Changes in the gut bacteria protect against stroke
Researchers at the University of Gothenburg, Sweden, and the Chalmers University of Technology, Sweden, demonstrate that an altered gut microbiota in humans is associated with symptomatic atherosclerosis and stroke. These findings are presented in a study published in Nature Communications on December 4.
The human body contains ten times more bacterial cells than human cells, most of which are found in the gut. These bacteria contain an enormous number of genes in addition to our host genome, and are collectively known as the gut metagenome.
How does the metagenome affect our health? This question is currently being addressed by researchers in the rapidly expanding field of metagenomic research. Several diseases have been linked to variations in the metagenome.
Researchers at Chalmers University of Technology and Sahlgrenska Academy, University of Gothenburg, now also show that changes in the gut metagenome can be linked to atherosclerosis and stroke.
The researchers compared a group of stroke patients with a group of healthy subjects and found major differences in their gut microbiota. In particular, they showed that genes required for the production of carotenoids were more frequently found in gut microbiota from healthy subjects. The healthy subjects also had significantly higher levels of a certain carotenoid in the blood than the stroke survivors.
Carotenoids are a type of antioxidant, and it has been claimed for many years that they protect against angina and stroke. Thus, the increased incidence of carotenoid-producing bacteria in the gut of healthy subjects may offer clues to explain how the gut metagenome affects disease states.
Carotenoids are marketed today as a dietary supplement. The market for them is huge, but clinical studies of their efficacy in protecting against angina and stroke have produced varying results.
Jens Nielsen, Professor of Systems Biology at Chalmers, says that it may be preferable to take probiotics instead – for example dietary supplements containing types of bacteria that produce carotenoids.
“Our results indicate that long-term exposure to carotenoids, through production by the bacteria in the digestive system, has important health benefits. These results should make it possible to develop new probiotics. We think that the bacterial species in the probiotics would establish themselves as a permanent culture in the gut and have a long-term effect”.
“By examining the patient’s bacterial microbiota, we should also be able to develop risk prognoses for cardiovascular disease”, says Fredrik Bäckhed, Professor of Molecular Medicine at the University of Gothenburg. “It should be possible to provide completely new disease-prevention options”.
The researchers have now started a company, Metabogen, to further develop their discoveries relating to the metagenome. Their success is based on close cooperation between engineers, microbiologists and doctors.
Jens Nielsen and Fredrik Bäckhed both agree that one of the challenges in the rapidly developing area of metagenomics is its multidisciplinary facets, requiring novel collaborations and merging of research fields.
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